The opposite effects of acute and chronic alcohol on lipopolysaccharide-induced inflammation are linked to IRAK-M in human monocytes.
- Authors
- Mandrekar, Pranoti; Bala, Shashi; Catalano, Donna; Kodys, Karen; Szabo, Gyongyi
- Year
- 2009
- Journal
- Journal of immunology (Baltimore, Md. : 1950)
- PMID
- 19561104
- DOI
- 10.4049/jimmunol.0803206
- PMCID
- PMC3845821
Impaired host defense after alcohol use is linked to altered cytokine production, however, acute and chronic alcohol differently modulate monocyte/macrophage activation. We hypothesized that in human monocytes, acute alcohol induces hyporesponsiveness to LPS, resulting in decreased TNF-alpha, whereas chronic alcohol increases TNF-alpha by sensitization to LPS. We found that acute alcohol increased IL-1R-associated kinase-monocyte (IRAK-M), a negative regulator of IRAK-1, in human monocytes. This was associated with decreased IkappaB alpha kinase activity, NFkappaB DNA binding, and NFkappaB-driven reporter activity after LPS stimulation. In contrast, chronic alcohol decreased IRAK-M expression but increased IRAK-1 and IKK kinase activities, NFkappaB DNA binding, and NFkappaB-reporter activity. Inhibition of IRAK-M in acute alcohol-exposed monocytes using small interfering RNA restored the LPS-induced TNF-alpha production whereas over-expression of IRAK-M in chronic alcohol macrophages prevented the increase in TNF-alpha production. Addition of inhibitors of alcohol metabolism did not alter LPS signaling and TNF-alpha production during chronic alcohol exposure. IRAK-1 activation induces MAPKs that play an important role in TNF-alpha induction. We determined that acute alcohol decreased but chronic alcohol increased activation of ERK in monocytes and ERK inhibitor, PD98059, prevented the chronic alcohol-induced increase in TNF-alpha. In summary, inhibition of LPS-induced NFkappaB and ERK activation by acute alcohol leads to hyporesponsiveness of monocytes to LPS due to increased IRAK-M. In contrast, chronic alcohol sensitizes monocytes to LPS through decreased IRAK-M expression and activation of NFkappaB and ERK kinases. Our data indicate that IRAK-M is a central player in the opposite regulation of LPS signaling by different lengths of alcohol exposure in monocytes.
Acute alcohol decreases but chronic alcohol treatment of human monocytes increases LPS-induced TNF-α production. A, Human monocytes were exposed to 25 mM alcohol (Et) from 1 to 7 days followed by LPS (100 ng/ml) treatment for 18 h and detection of TNF-α in the cell-free supernatants by ELISA. Mean values of TNF-α (pg/ml/106 cells) ± SE from a total of ten individuals are shown (compared with LPS; *, p < 0.001). B, LPS (100 ng/ml) treatment for 3 h and TNF-α mRNA determination by real-time PCR using specific TNF-α primers as described in Materials and Methods. The bar graph represents fold induction of mRNA ± SE (compared with LPS; *, p < 0.01; **, p < 0.001; n = 6).
Alcohol alters IRAK-M and IRAK-1 levels without any effect on CD14 and TLR4 expression. A, Human monocytes were either exposed to 25 mM alcohol (Et) for 1 day (acute) or 7 days (chronic), stained with CD14 and TLR4 Abs, and analyzed by flow cytometry. Iso-type IgG Abs were used as negative controls. B, Human monocytes were exposed to 25 mM alcohol for 7 days (Chr) followed by LPS (100 ng/ml) for 15 min. Immunoprecipitation (IP) of the cytoplasmic extracts with IRAK-1 Ab in lysis buffer was conducted as described in Materials and Methods. The kinase assay was performed with MBP (myelin basic protein) as substrate. The proteins were separated on SDS-PAGE and the gel depicts the 32P-phosphorylated MBP. Equal protein in the IP samples was determined by immunoblotting (WB) with IRAK-1 Abs. The bar graph below represents the cpm incorporated in the substrate as measured by scintillation counter. (compared with unst; *, p < 0.01; compared with LPS; **, p < 0.05; n = 4). C, Human monocytes were exposed to 25 mM alcohol (Et) for 1 day (Ac) or 7 days (Chr) followed by LPS (100 ng/ml) treatment for 6 h and IRAK-M mRNA determination by real-time PCR using specific IRAK-M primers as described in Materials and Methods. The bar graph represents fold induction of mRNA ± SE (compared with unst; *, p < 0.01; compared with LPS; **, p < 0.02; n = 4). D, Monocytes were exposed to 25 mM alcohol (Et) for 1 day (Ac) or 7 days (Chr) followed by LPS (100 ng/ml) treatment for 24 h and IRAK-M protein levels determined by immunoblotting using anti-IRAK-M Abs as described in Materials and Methods. Equal loading of protein is demonstrated using an internal control anti-β-actin Ab.
IRAK-M expression regulates TNF-α during alcohol exposure. A, Raw macrophages (control cells) were transfected with control siRNA (scr) and IRAK-M-specific siRNA and after 48 h exposed to 25 mM alcohol followed by LPS for 6 h. Total RNA extracts were analyzed for IRAK-M mRNA by real time PCR and bar graph (upper panel) represented as percentage of IRAK-M gene expression (compared with control; *, p < 0.009). Whole cell lysates in the presence or absence of LPS for 6 h were analyzed for IRAK-M protein by Western blot analysis (middle panel) and supernatants analyzed for TNF-α production by ELISA (lower panel). Mean values of TNF-α (pg/ml/106 cells) ± SE from three experiments are shown (compared with control siRNA; #, p < 0.007; **, p < 0.01). B, Raw 264.7 macrophages were exposed to chronic alcohol for 7 days, transfected with either control vector or IRAK-M overexpression vector (Origene) for 36 h and treated without (inset graph) or with LPS for 6 h. Whole cell lysates were subject to Western blotting using anti- IRAK-M (upper panel) Ab and supernatents were analyzed for TNF-α by ELISA (lower panel). Mean values of TNF-α (pg/ml/106 cells) ± SE from a three experiments are shown (compared with vector control; *, p < 0.01; **, p < 0.001).
Acute alcohol decreases whereas chronic alcohol increases LPS-induced IKK kinase activity in human monocytes. Human monocytes were exposed to alcohol (Et) for 1 day (Ac) or 7 days (Chr) followed by stimulation with LPS (100 ng/ml) for 15 min. IP of the cytoplasmic extracts with IKKβ Abs in lysis buffer was followed by kinase assays using the GST-IκBα as substrate as described in Materials and Methods. The proteins were separated on SDS-PAGE and the gels depict the 32P-phosphorylated GST-IκBα. Equal protein loading in the input samples was determined by immunoblotting with β-actin Ab. The bar graph represents the cpm incorporated in the substrate as measured by scintillation counter. (compared with unst; *, p < 0.05; compared with LPS; #, p < 0.05; **, p < 0.01; n = 3).
Inhibition of MAPK-ERK activation by acute alcohol whereas chronic alcohol increases phospho-ERK levels in monocytes. Monocytes were exposed to 25 mM alcohol (Et) for 1 day (Ac) or 7 days (Chr) followed by LPS (100 ng/ml) treatment for 15 min. A, Total and phospho-ERK, phospho-p38 and phospho-JNK protein levels determined by immunoblotting using anti-specific phospho-antibodies as described in Materials and Methods. B, Mean density units ± SE of the phospho-ERK bands from a total of six individuals is shown. (compared with LPS; *, p < 0.05; #, p < 0.02, n = 6). C, Monocytes were exposed to 25 mM alcohol (Et) for 7 days (Chr) followed by incubation with ERK inhibitor (PD98059, 50 μM) for 4 h and stimulation with LPS (100 ng/ml) for 18 h. Cell-free supernatants were collected and assayed for TNF-α in an ELISA. The data are represented as mean ± SE (compared with LPS; **, p < 0.001; compared with Chr Et plus LPS; *, p < 0.02, n = 6).
Alcohol exposure, acute and chronic, promotes LPS-induced IκBα degradation in monocytes. Monocytes were exposed to alcohol for 1 (Ac), 4, and 7 days followed by simulation with LPS (100 ng/ml) for 60 min. Cytoplasmic extracts were prepared and immunoblotted with total IκBα Ab. The bar graph represents mean density units ± SE from a total of six individuals (compared with LPS; *, p < 0.02, n = 6).
Opposite effects of acute and chronic alcohol exposure on NFκB binding activity is independent of alcohol metabolism in human monocytes. A, Monocytes were exposed to alcohol for 1 (Ac), 4, and 7 days followed by simulation with LPS (100 ng/ml) for 60 min. NFκB was detected in the nuclear extracts by EMSA using a 32P-labeled double-stranded NFκB oli-gonucleotide. The bar graph shows mean density ± SE of a total of six individuals (compared with LPS; *, p < 0.01). B, RAW 264.7 macrophages were exposed to alcohol (Et) for 1 (ac) or 4 days (chr) and then transiently transfected with NFκB reporter gene constructs carrying five tandem copies of the NFκB binding site in front of the firefly luciferase gene and the Renilla luciferase construct. At 24 h after transfection, cells were treated with LPS (100 ng/ml) for 8 h. Cells were then lysed to determine firefly luciferase activity and normalized to the Renilla luciferase activity. The bar graph represents fold activation of the luciferase gene as compared with the unstimulated control of a total of three experiments. (compared with LPS; *, p < 0.01; **, p < 0.02, n = 3). C, Monocytes were exposed to 25 mM alcohol (Et) for 1 to 7 days and CYP2E1 protein levels determined by immunoblotting using anti-CYP2E1 Abs as described in Materials and Methods. The bar graph represents mean density ± SE of a total of six individuals. D, Monocytes were exposed to alcohol for 7 days along with 4-methyl-prazole or cyanamide followed by stimulation with LPS (100 ng/ml) for 60 min. NFκB was detected in the nuclear extracts by EMSA using a 32P-labeled double-stranded NFκB oligonucleotide. The bar graph shows mean density ± SE of a total of six individuals (compared with unst; *, p < 0.001; compared with LPS; **, p < 0.001). E, Monocytes were exposed to 25 mM alcohol (Et) for 7 days (Chr) along with 4-methyl-prazole or cyanamide followed by stimulation with LPS (100 ng/ml) for 18 h. Cell-free supernatants were collected and assayed for TNF-α in an ELISA. The data are represented as mean ± SE (compared with LPS; *, p < 0.001, n = 6).
Alcohol, based on the length of exposure, alters IRAK-M to differently regulate LPS signaling in human monocytes. Acute alcohol exposure induces whereas chronic alcohol decreases IRAK-M in human monocytes to either reduce or augment activity of down-stream LPS signaling molecules IRAK-1, IKK, ERK, and NFκB, and finally TNF-α production, respectively.
| Name | Type |
|---|---|
| 4-methyl pyrazole local | drug |
| 4-methylpyrazole local | drug |
| ACTB | gene |
| acute alcohol local | drug |
| Acute alcohol local | drug |
| Acute alcohol induced immunosuppression local | phenotype |
| Acute anti-inflammatory phenotype local | phenotype |
| acute withdrawal | phenotype |
| Advanced cirrhosis local | phenotype |
| alcohol | phenotype |
| alcohol abuse | phenotype |
| alcoholic liver disease | phenotype |
| Alcohol-related liver injury local | phenotype |
| aldehyde dehydrogenase | gene |
| Alveolar macrophages local | phenotype |
| animal models | cohort |
| Antibiotics local | drug |
| anti-rabbit IgG beads local | drug |
| AP-1 | drug |
| ATP | drug |
| Cd14 | gene |
| chemiluminescence assay reagents local | drug |
| chronic alcoholism | phenotype |
| Chronic alcohol-mediated liver disease local | phenotype |
| Chronic hyperinflammatory phenotype local | phenotype |
| Circulating T cells local | cohort |
| CSF2 local | gene |
| cyanamide | drug |
| CYP2E1 | gene |
| DTT | drug |
| Dual Glo Luciferase Assay reagent local | drug |
| Dulbecco's Modified Eagle Medium | drug |
| ERK kinase inhibitor local | drug |
| ERK MAPK local | drug |
| ethanol consumption | phenotype |
| FBS | drug |
| fetal bovine serum | drug |
| Ficoll-Hypaque local | drug |
| Firefly luciferase local | gene |
| fluorochrome-conjugated mAbs local | drug |
| Fugene 6 | drug |
| GAPDH | gene |
| Glutathione availability local | phenotype |
| GM-CSF local | phenotype |
| GM-CSF receptors local | phenotype |
| GST-IκBα local | drug |
| healthy controls | cohort |
| HEPES | drug |
| HRP | drug |
| human | cohort |
| human 18S primers local | drug |
| human monocytes local | cohort |
| human monocytes local | phenotype |
| Human monocytes local | cohort |
| Human peripheral blood monocytes local | cohort |
| human TNF-α primers local | drug |
| Hyperinflammatory state local | phenotype |
| Hyporesponsiveness to LPS local | phenotype |
| iCycler iQ Real-Time Detection System local | drug |
| IFNG | gene |
| IKBKB | gene |
| IL1B | gene |
| Immune phenotype of peripheral blood monocytes local | phenotype |
| Immunosuppression local | phenotype |
| Increased sensitization to LPS local | phenotype |
| increased susceptibility to infections local | phenotype |
| Increased susceptibility to infections local | phenotype |
| Increased TNF-α expression local | phenotype |
| Increased TNF-α production local | phenotype |
| inflammation | phenotype |
| inflammatory cytokine gene expression local | phenotype |
| Intracellular Ca2+ concentration local | phenotype |
| IRAK | gene |
| IRAK-1 local | gene |
| IRAK1 local | gene |
| IRAK-1 kinase activity local | phenotype |
| IRAK3 local | gene |
| IRAK4 local | gene |
| IRAK-M local | gene |
| IRAKM local | gene |
| IRAK-M primers local | drug |
| IRF3 | gene |
| JNK local | drug |
| JNK | gene |
| Kupffer cells local | cohort |
| Kupffer cells local | phenotype |
| Lipofectamine | drug |
| lipopolysaccharide | drug |
| lipopolysaccharide (LPS) | drug |
| liver injury | phenotype |
| LPS | drug |
| LPS hyporesponsiveness local | phenotype |
| LPS hyporesponsive state local | phenotype |
| LPS sensitization local | phenotype |
| MAPK | gene |
| Mapk1 | gene |
| MAPK3 | gene |
| MAPK8 | gene |
| MAPK-ERK local | gene |
| MBP | gene |
| MgCl2 | drug |
| murine | cohort |
| Myd88 | gene |
| NFKB1 | gene |
| NFkB activation local | phenotype |
| NFKBIA | gene |
| NF-κB | gene |
| NFκB | gene |
| NFκB activation local | phenotype |
| NFκB oligo local | drug |
| NFκB oligonucleotide local | drug |
| NF-κB p50 homodimer local | gene |
| NFκB p65 local | gene |
| NK cells | cohort |
| nonfat dried milk local | drug |
| oxidative stress | phenotype |
| oxidative stress related liver injury local | phenotype |
| p38 MAPK | gene |
| paraformaldehyde | drug |
| Patients with advanced cirrhosis local | cohort |
| pCMV6-XL-4 local | drug |
| PD98059 | drug |
| Peripheral blood monocytes local | phenotype |
| Phagocytic function local | phenotype |
| pro-inflammatory cytokines | phenotype |
| proinflammatory response | phenotype |
| p(κB)5-Luc local | drug |
| RAW 264.7 local | cohort |
| RAW 264.7 cells local | cohort |
| Raw 264.7 macrophages local | cohort |
| reactive oxygen species | drug |
| Renilla luciferase | gene |
| Reverse Transcription System local | drug |
| RNase-Free DNase set | drug |
| RNeasy Mini kit | drug |
| rRNA | drug |
| Sensitization to LPS local | phenotype |
| septic shock local | phenotype |
| siRNA | drug |
| SOCS1 | gene |
| Splenic macrophages local | phenotype |
| Susceptibility to infections local | phenotype |
| SYP | gene |
| TBK1 local | gene |
| TBP | gene |
| TICAM1 local | gene |
| Tlr2 | gene |
| Tlr4 | gene |
| TLR tolerance local | phenotype |
| TNF | gene |
| TNFAIP3 | gene |
| TNF production local | phenotype |
| TNF-α | drug |
| TNF-α local | phenotype |
| TNF-α production local | phenotype |
| TOLLIP local | gene |
| TRAF6 local | gene |
| Tris-HCl | drug |
| Triton X-100 | drug |
| Tween-20 | drug |
| γ32P ATP local | drug |
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|---|---|---|---|---|
| Acute changes in immune biomarkers under low- and moderate-dose alcohol in light and heavy drinkers: A randomized, placebo-controlled trial. | Monnig MA et al. | — | 2025 | → |
| Alcohol consumption and immune cell profiles: Insights from the Framingham Heart Study. | Ragab AAY et al. | — | 2025 | → |
| Alcohol-induced susceptibility to pulmonary bacterial infections: A narrative review. | Gobalakrishnan T et al. | — | 2025 | → |
| Origin, Function, and Implications of Intestinal and Hepatic Macrophages in the Pathogenesis of Alcohol-Associated Liver Disease. | Hu Y et al. | — | 2025 | → |
| Short-term heavy drinking in a non-human primate model skews monocytes toward a hypo-inflammatory phenotype. | Blanton MB et al. | — | 2025 | → |
| Adolescent intermittent ethanol (AIE) produces lasting, sex-specific changes in rat body fat independent of changes in white blood cell composition. | Vore AS et al. | — | 2024 | → |
| IL-1 receptor-associated kinase family proteins: An overview of their role in liver disease. | Wang ZY et al. | — | 2024 | → |
| Linking alcohol use to Alzheimer's disease: Interactions with aging and APOE along immune pathways. | Monnig M et al. | — | 2024 | → |
| Replenishing IRAK-M expression in retinal pigment epithelium attenuates outer retinal degeneration. | Liu J et al. | — | 2024 | → |
| Role of Myeloid Cell-Specific Adenylyl Cyclase Type 7 in Lipopolysaccharide- and Alcohol-Induced Immune Responses. | Hu Y et al. | — | 2024 | → |
| The Role of Cytokines in the Pathogenesis and Treatment of Alcoholic Liver Disease. | Scarlata GGM et al. | — | 2024 | → |
| Alcohol consumption modulates Candida albicans-induced oral carcinogenesis and progression. | O'Grady I et al. | — | 2023 | → |
| A novel score of IL-13 and age predicts 90-day mortality in severe alcohol-associated hepatitis: A multicenter plasma biomarker analysis. | Tornai D et al. | — | 2023 | → |
| Direct and indirect effects of alcohol and its toxic metabolite acetaldehyde on human esophageal myofibroblasts and epithelial cells. | Khalatbari A et al. | — | 2023 | → |
| Exacerbating effects of single-dose acute ethanol exposure on neuroinflammation and amelioration by GPR110 (ADGRF1) activation. | Banerjee S et al. | — | 2023 | → |
| Mitochondrial Dysfunction: At the Nexus between Alcohol-Associated Immunometabolic Dysregulation and Tissue Injury. | Siggins RW et al. | — | 2023 | → |
| An exploratory study of pro-inflammatory cytokines in individuals with alcohol use disorder: MCP-1 and IL-8 associated with alcohol consumption, sleep quality, anxiety, depression, and liver biomarkers. | Kazmi N et al. | — | 2022 | → |
| Chronic Alcohol Exposure Among People Living with HIV Is Associated with Innate Immune Activation and Alterations in Monocyte Phenotype and Plasma Cytokine Profile. | Underwood ML et al. | — | 2022 | → |
| HCV and tumor-initiating stem-like cells. | Machida K | — | 2022 | → |
| Prenatal and adolescent alcohol exposure programs immunity across the lifespan: CNS-mediated regulation. | Deak T et al. | — | 2022 | → |
| Prospective associations between multiple lifestyle behaviors and depressive symptoms. | Werneck AO et al. | — | 2022 | → |
| Transcriptional and Epigenetic Regulation of Monocyte and Macrophage Dysfunction by Chronic Alcohol Consumption. | Malherbe DC et al. | — | 2022 | → |
| Acetaldehyde exposure underlies functional defects in monocytes induced by excessive alcohol consumption. | Shiba S et al. | — | 2021 | → |
| Emerging Comorbidities in Inflammatory Bowel Disease: Eating Disorders, Alcohol and Narcotics Misuse. | Kuźnicki P et al. | — | 2021 | → |
| Ethanol: striking the cardiovascular system by harming the gut microbiota. | Silva CBP et al. | — | 2021 | → |
| IL-10 normalizes aberrant amygdala GABA transmission and reverses anxiety-like behavior and dependence-induced escalation of alcohol intake. | Patel RR et al. | — | 2021 | → |
| Moderate Beer Intake Downregulates Inflammasome Pathway Gene Expression in Human Macrophages. | Muñoz-Garcia N et al. | — | 2021 | → |
| Myeloid Endoplasmic Reticulum Resident Chaperone GP96 Facilitates Inflammation and Steatosis in Alcohol-Associated Liver Disease. | Ratna A et al. | — | 2021 | → |
| Nutrition and the Covid-19 pandemic: Three factors with high impact on community health. | Iaccarino Idelson P et al. | — | 2021 | → |
| Transcriptional, epigenetic, and functional reprogramming of blood monocytes in non-human primates following chronic alcohol drinking | Lewis SA et al. | — | 2021 | — |
| Transcriptional, Epigenetic, and Functional Reprogramming of Monocytes From Non-Human Primates Following Chronic Alcohol Drinking. | Lewis SA et al. | — | 2021 | → |
| TSPAN5 influences serotonin and kynurenine: pharmacogenomic mechanisms related to alcohol use disorder and acamprosate treatment response. | Ho MF et al. | — | 2021 | → |
| Acute Alcohol Intoxication Impairs Sonic Hedgehog-Gli1 Signaling and Activation of Primitive Hematopoietic Precursor Cells in the Early Stage of Host Response to Bacteremia. | Shi X et al. | — | 2020 | → |
| Analysis of interleukin-1 receptor associated kinase-3 (IRAK3) function in modulating expression of inflammatory markers in cell culture models: A systematic review and meta-analysis. | Nguyen TH et al. | — | 2020 | → |
| Clinical characteristics analysis of 1180 patients with hepatocellular carcinoma secondary to hepatitis B, hepatitis C and alcoholic liver disease. | Zhao H et al. | — | 2020 | → |
| Daily alcohol intake triggers aberrant synaptic pruning leading to synapse loss and anxiety-like behavior. | Socodato R et al. | — | 2020 | → |
| Extracellular vesicle-associated soluble CD163 and CD206 in patients with acute and chronic inflammatory liver disease. | Nielsen MC et al. | — | 2020 | → |
| Gut microbiota in non-alcoholic fatty liver disease and alcohol-related liver disease: Current concepts and perspectives. | Arab JP et al. | — | 2020 | → |
| Healthful aging mediated by inhibition of oxidative stress. | Vatner SF et al. | — | 2020 | → |
| Opening a Window on Attention: Adjuvant Therapies for Inflammatory Bowel Disease. | Wang Q et al. | — | 2020 | → |
| Role of Mesencephalic Astrocyte-Derived Neurotrophic Factor in Alcohol-Induced Liver Injury. | Chhetri G et al. | — | 2020 | → |
| Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response. | Ng HP et al. | — | 2020 | → |
| Significance of Markers of Monocyte Activation (CD163 and sCD14) and Inflammation (IL-6) in Patients Admitted for Alcohol Use Disorder Treatment. | García-Calvo X et al. | — | 2020 | → |
| The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors. | Deshpande RP et al. | — | 2020 | → |
| Chronic heavy drinking drives distinct transcriptional and epigenetic changes in splenic macrophages. | Sureshchandra S et al. | — | 2019 | → |
| Delayed spontaneous hepatitis C virus elimination in a renal transplant patient following graft rejection. | Mori Ubaldini F et al. | — | 2019 | → |
| Dose-dependent effects of chronic alcohol drinking on peripheral immune responses. | Sureshchandra S et al. | — | 2019 | → |
| Innate Immunity and Alcohol. | Kany S et al. | — | 2019 | → |
| Integrative In Silico and In Vitro Transcriptomics Analysis Revealed Gene Expression Changes and Oncogenic Features of Normal Cholangiocytes after Chronic Alcohol Exposure. | Chujan S et al. | — | 2019 | → |
| Murine macrophage autophagy protects against alcohol-induced liver injury by degrading interferon regulatory factor 1 (IRF1) and removing damaged mitochondria. | Liang S et al. | — | 2019 | → |
| Pharmacological Inhibition of CCR2/5 Signaling Prevents and Reverses Alcohol-Induced Liver Damage, Steatosis, and Inflammation in Mice. | Ambade A et al. | — | 2019 | → |
| Rapid alterations in neuroimmune gene expression after acute ethanol: Timecourse, sex differences and sensitivity to cranial surgery. | Gano A et al. | — | 2019 | → |
| Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease. | Wang H et al. | — | 2019 | → |
| Salidroside Inhibits Lipopolysaccharide-ethanol-induced Activation of Proinflammatory Macrophages via Notch Signaling Pathway. | Li JS et al. | — | 2019 | → |
| Status of inflammation and alcohol use in a 6-month follow-up study of patients with major depressive disorder. | Archer M et al. | — | 2019 | → |
| Using human stem cells as a model system to understand the neural mechanisms of alcohol use disorders: Current status and outlook. | Scarnati MS et al. | — | 2019 | → |
| Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg. | Arab JP et al. | — | 2018 | → |
| Microglia and alcohol meet at the crossroads: Microglia as critical modulators of alcohol neurotoxicity. | Henriques JF et al. | — | 2018 | → |
| Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF-<i>κ</i>B Signaling Pathways in Mice. | Xu L et al. | — | 2018 | → |
| Small heterodimer partner deficiency exacerbates binge drinking‑induced liver injury via modulation of natural killer T cell and neutrophil infiltration. | Go MJ et al. | — | 2018 | → |
| Sophocarpine Attenuates LPS-Induced Liver Injury and Improves Survival of Mice through Suppressing Oxidative Stress, Inflammation, and Apoptosis. | Jiang Z et al. | — | 2018 | → |
| Young alcohol binge drinkers have elevated blood endotoxin, peripheral inflammation and low cortisol levels: neuropsychological correlations in women. | Orio L et al. | — | 2018 | → |
| Alcohol, aging, and innate immunity. | Boule LA et al. | — | 2017 | → |
| Alcohol-induced miR-155 and HDAC11 inhibit negative regulators of the TLR4 pathway and lead to increased LPS responsiveness of Kupffer cells in alcoholic liver disease. | Bala S et al. | — | 2017 | → |
| Alcohol Modulation of the Postburn Hepatic Response. | Chen MM et al. | — | 2017 | → |
| Epigenetic Interactions between Alcohol and Cannabinergic Effects: Focus on Histone Modification and DNA Methylation. | Parira T et al. | — | 2017 | → |
| Frontline Science: ATF3 is responsible for the inhibition of TNF-α release and the impaired migration of acute ethanol-exposed monocytes and macrophages. | Hu C et al. | — | 2017 | → |
| Gut-liver axis and sterile signals in the development of alcoholic liver disease. | Szabo G et al. | — | 2017 | → |
| IL-1 receptor like 1 protects against alcoholic liver injury by limiting NF-κB activation in hepatic macrophages. | Wang M et al. | — | 2017 | → |
| Immune activation and neuroinflammation in alcohol use and HIV infection: evidence for shared mechanisms. | Monnig MA | — | 2017 | → |
| In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence. | Hillmer AT et al. | — | 2017 | → |
| Long-Term Ethanol Exposure Decreases the Endotoxin-Induced Hepatic Acute Phase Response in Rats. | Glavind E et al. | — | 2017 | → |
| Microglial depletion alters the brain neuroimmune response to acute binge ethanol withdrawal. | Walter TJ et al. | — | 2017 | → |
| Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome. | Hoyt LR et al. | — | 2017 | → |
| Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System. | Rachdaoui N et al. | — | 2017 | → |
| Quantity of alcohol drinking positively correlates with serum levels of endotoxin and markers of monocyte activation. | Liangpunsakul S et al. | — | 2017 | → |
| The role of smoking and alcohol behaviour in the management of inflammatory bowel disease. | Khasawneh M et al. | — | 2017 | → |
| Alcohol abuse and smoking alter inflammatory mediator production by pulmonary and systemic immune cells. | Gaydos J et al. | — | 2016 | → |
| Alcohol and lung injury and immunity. | Yeligar SM et al. | — | 2016 | → |
| Alcohol use predicts elevation in inflammatory marker soluble CD14 in men living with HIV. | Monnig MA et al. | — | 2016 | → |
| Association between circulating inflammatory molecules and alcoholic liver disease in men. | Qu BG et al. | — | 2016 | → |
| Changes in gut toll-like receptor-4 and nod-like receptor family pyrin domain containing-3 innate pathways in liver cirrhosis rats with bacterial translocation. | Liu L et al. | — | 2016 | → |
| Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling. | Zhong W et al. | — | 2016 | → |
| Effects of alcohol withdrawal on monocyte subset defects in chronic alcohol users. | Donnadieu-Rigole H et al. | — | 2016 | → |
| Factors associated with spontaneous clearance of chronic hepatitis C virus infection. | Bulteel N et al. | — | 2016 | → |
| IRAKM-Mincle axis links cell death to inflammation: Pathophysiological implications for chronic alcoholic liver disease. | Zhou H et al. | — | 2016 | → |
| <i>Strongyloides stercoralis</i> Infection in Alcoholic Patients. | Teixeira MC et al. | — | 2016 | → |
| Malondialdehyde-Acetaldehyde-Adducted Surfactant Protein Alters Macrophage Functions Through Scavenger Receptor A. | Sapkota M et al. | — | 2016 | → |
| Microbiota-based treatments in alcoholic liver disease. | Sung H et al. | — | 2016 | → |
| Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the Relationship to Psychiatric Assessments. | Manzardo AM et al. | — | 2016 | → |
| Neuroimmune Interface in the Comorbidity between Alcohol Use Disorder and Major Depression. | Neupane SP | — | 2016 | → |
| Opposing effects of alcohol on the immune system. | Barr T et al. | — | 2016 | → |
| Sexual Dimorphism in Alcohol Induced Adipose Inflammation Relates to Liver Injury. | Fulham MA et al. | — | 2016 | → |
| Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis. | Lin R et al. | — | 2015 | → |
| Acute and Chronic Ethanol Administration Differentially Modulate Hepatic Autophagy and Transcription Factor EB. | Thomes PG et al. | — | 2015 | → |
| Alcohol-induced miR-27a regulates differentiation and M2 macrophage polarization of normal human monocytes. | Saha B et al. | — | 2015 | → |
| Alcohol's Effect on Host Defense. | Szabo G et al. | — | 2015 | → |
| Alcohol Versus Cannabinoids: A Review of Their Opposite Neuro-Immunomodulatory Effects and Future Therapeutic Potentials. | Nair MP et al. | — | 2015 | → |
| Chronic alcohol exposure exacerbates inflammation and triggers pancreatic acinar-to-ductal metaplasia through PI3K/Akt/IKK. | Huang X et al. | — | 2015 | → |
| Effects of probiotics (cultured Lactobacillus subtilis/Streptococcus faecium) in the treatment of alcoholic hepatitis: randomized-controlled multicenter study. | Han SH et al. | — | 2015 | → |
| Hepatitis C, innate immunity and alcohol: friends or foes? | Osna NA et al. | — | 2015 | → |
| Inflammatory markers among adolescents and young adults with bipolar spectrum disorders. | Goldstein BI et al. | — | 2015 | → |
| Intestinal mucosal barrier dysfunction participates in the progress of nonalcoholic fatty liver disease. | Mao JW et al. | — | 2015 | → |
| Krüppel-like factor 4 is a transcriptional regulator of M1/M2 macrophage polarization in alcoholic liver disease. | Saha B et al. | — | 2015 | → |
| MicroRNAs in alcoholic liver disease. | Szabo G et al. | — | 2015 | → |
| Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice. | Hao L et al. | — | 2015 | → |
| The role of Interleukin Receptor Associated Kinase (IRAK)-M in regulation of myofibroblast phenotype in vitro, and in an experimental model of non-reperfused myocardial infarction. | Saxena A et al. | — | 2015 | → |
| TLR2 and TLR4 Expression and Inflammatory Cytokines are Altered in the Airway Epithelium of Those with Alcohol Use Disorders. | Bailey KL et al. | — | 2015 | → |
| Vibrio cholerae porin OmpU induces LPS tolerance by attenuating TLR-mediated signaling. | Sakharwade SC et al. | — | 2015 | → |
| Acute alcohol exposure has an independent impact on C-reactive protein levels, neutrophil CD64 expression, and subsets of circulating white blood cells differentiated by flow cytometry in nontrauma patients. | Gacouin A et al. | — | 2014 | → |
| Chronic ethanol feeding modulates inflammatory mediators, activation of nuclear factor-κB, and responsiveness to endotoxin in murine Kupffer cells and circulating leukocytes. | Maraslioglu M et al. | — | 2014 | → |
| Effects of Korean Red Ginseng (Panax ginseng), urushiol (Rhus vernicifera Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) on the gut-liver axis of alcoholic liver disease. | Bang CS et al. | — | 2014 | → |
| Effects of selenium-enriched Agaricus blazei Murill on liver metabolic dysfunction in mice, a comparison with selenium-deficient Agaricus blazei Murill and sodium selenite. | Yu L et al. | — | 2014 | → |
| Immunity and inflammatory signaling in alcoholic liver disease. | Mandrekar P et al. | — | 2014 | → |
| Moderate alcohol induces stress proteins HSF1 and hsp70 and inhibits proinflammatory cytokines resulting in endotoxin tolerance. | Muralidharan S et al. | — | 2014 | → |
| The functional role of microRNAs in alcoholic liver injury. | McDaniel K et al. | — | 2014 | → |
| Alcohol facilitates HCV RNA replication via up-regulation of miR-122 expression and inhibition of cyclin G1 in human hepatoma cells. | Hou W et al. | — | 2013 | → |
| Binge ethanol and liver: new molecular developments. | Shukla SD et al. | — | 2013 | → |
| Effect of bacterial pneumonia on lung simian immunodeficiency virus (SIV) replication in alcohol consuming SIV-infected rhesus macaques. | Nelson S et al. | — | 2013 | → |
| Effects of alcohol on the endocrine system. | Rachdaoui N et al. | — | 2013 | → |
| Ethanol facilitates hepatitis C virus replication via up-regulation of GW182 and heat shock protein 90 in human hepatoma cells. | Bukong TN et al. | — | 2013 | → |
| MFG-E8 and HMGB1 are involved in the mechanism underlying alcohol-induced impairment of macrophage efferocytosis. | Wang X et al. | — | 2013 | → |
| Microarray characterization of gene expression changes in blood during acute ethanol exposure. | Kupfer DM et al. | — | 2013 | → |
| Patients with acute pancreatitis complicated by organ dysfunction show abnormal peripheral blood polymorphonuclear leukocyte signaling. | Oiva J et al. | — | 2013 | → |
| Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4 signaling in macrophages. | Sung NY et al. | — | 2013 | → |
| Response of Differentiated Human Airway Epithelia to Alcohol Exposure and <i>Klebsiella Pneumoniae</i> Challenge. | Raju SV et al. | — | 2013 | → |
| Role of IRAK-M in alcohol induced liver injury. | Wang Y et al. | — | 2013 | → |
| Sterile inflammation in the liver and pancreas. | Hoque R et al. | — | 2013 | → |
| Tumor-initiating stem-like cells and drug resistance: carcinogenesis through Toll-like receptors, environmental factors, and virus. | Machida K | — | 2013 | → |
| Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus. | Machida K et al. | — | 2012 | → |
| Chronic alcohol exposure, infection, extended circulating white blood cells differentiated by flow cytometry and neutrophil CD64 expression: a prospective, descriptive study of critically ill medical patients. | Gacouin A et al. | — | 2012 | → |
| Differences in lipopolysaccharide- and lipoteichoic acid-induced cytokine/chemokine expression. | Finney SJ et al. | — | 2012 | → |
| Ethanol suppresses phagosomal adhesion maturation, Rac activation, and subsequent actin polymerization during FcγR-mediated phagocytosis. | Karavitis J et al. | — | 2012 | → |
| Induction of Bcl-3 by acute binge alcohol results in toll-like receptor 4/LPS tolerance. | Bala S et al. | — | 2012 | → |
| Innate immunity and alcoholic liver disease. | Szabo G et al. | — | 2012 | → |
| IRAK-M modulates expression of IL-10 and cell surface markers CD80 and MHC II after bacterial re-stimulation of tolerized dendritic cells. | Cole TS et al. | — | 2012 | → |
| Oxidative stress and inflammation: essential partners in alcoholic liver disease. | Ambade A et al. | — | 2012 | → |
| The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension. | Seo YS et al. | — | 2012 | → |
| An essential role for monocyte chemoattractant protein-1 in alcoholic liver injury: regulation of proinflammatory cytokines and hepatic steatosis in mice. | Mandrekar P et al. | — | 2011 | → |
| Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats. | Husain K et al. | — | 2011 | → |
| Glycogen synthase kinase 3 involvement in the excessive proinflammatory response to LPS in patients with decompensated cirrhosis. | Coant N et al. | — | 2011 | → |
| Inhibition of TLR8- and TLR4-induced Type I IFN induction by alcohol is different from its effects on inflammatory cytokine production in monocytes. | Pang M et al. | — | 2011 | → |
| S-adenosylmethionine prevents the up regulation of Toll-like receptor (TLR) signaling caused by chronic ethanol feeding in rats. | Oliva J et al. | — | 2011 | → |
| The unfolding web of innate immune dysregulation in alcoholic liver injury. | Szabo G et al. | — | 2011 | → |
| Toll-like receptor 4 signalling is specifically TGF-beta-activated kinase 1 independent in synovial fibroblasts. | Geurts J et al. | — | 2011 | → |
| Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease. | Bala S et al. | — | 2011 | → |
| Alcoholic liver disease and the gut-liver axis. | Szabo G et al. | — | 2010 | → |
| Alcohol, nutrition and liver cancer: role of Toll-like receptor signaling. | French SW et al. | — | 2010 | → |
| Alcohol takes the toll on immune function. | Stadlbauer V et al. | — | 2010 | → |
| Anti-inflammatory pathways and alcoholic liver disease: role of an adiponectin/interleukin-10/heme oxygenase-1 pathway. | Mandal P et al. | — | 2010 | → |
| Focus on: Alcohol and the immune system. | Molina PE et al. | — | 2010 | → |
| Gut-liver axis and sensing microbes. | Szabo G et al. | — | 2010 | → |
| Patients with acute pancreatitis complicated by organ failure show highly aberrant monocyte signaling profiles assessed by phospho-specific flow cytometry. | Oiva J et al. | — | 2010 | → |
| Secreted monocytic miR-150 enhances targeted endothelial cell migration. | Zhang Y et al. | — | 2010 | → |
| The potential of cytokines as safety biomarkers for drug-induced liver injury. | Laverty HG et al. | — | 2010 | → |
| TLRs, Alcohol, HCV, and Tumorigenesis. | Machida K | — | 2010 | → |
| Toll-like receptors in the pathogenesis of alcoholic liver disease. | Petrasek J et al. | — | 2010 | → |