Gemfibrozil ameliorates relapsing-remitting experimental autoimmune encephalomyelitis independent of peroxisome proliferator-activated receptor-alpha.
paper
Cited
Public
Unavailable
- Authors
- Dasgupta, Subhajit; Roy, Avik; Jana, Malabendu; Hartley, Dean M; Pahan, Kalipada
- Year
- 2007
- Journal
- Molecular pharmacology
- PMID
- 17625103
- DOI
- 10.1124/mol.106.033787
The present study underlines the importance of gemfibrozil, a lipid-lowering drug and an activator of peroxisome proliferator-activated receptor-alpha (PPAR-alpha), in inhibiting the disease process of adoptively transferred experimental allergic encephalomyelitis (EAE), an animal model of relapsing-remitting multiple sclerosis. Clinical symptoms of EAE, infiltration of mononuclear cells, and demyelination were significantly lower in SJL/J female mice receiving gemfibrozil through food chow than those without gemfibrozil. It is noteworthy that the drug was equally effective in treating EAE in PPAR-alpha wild-type as well as knockout mice. Gemfibrozil also inhibited the encephalitogenicity of MBP-primed T cells and switched the immune response from a Th1 to a Th2 profile independent of PPAR-alpha. Gemfibrozil consistently inhibited the expression and DNA-binding activity of T-bet, a key regulator of interferon-gamma (IFN-gamma) expression and stimulated the expression and DNA-binding activity of GATA3, a key regulator of IL-4. Gemfibrozil treatment decreased the number of T-bet-positive T cells and increased the number of GATA3-positive T cells in spleen of donor mice. The histological and immunohistochemical analyses also demonstrate the inhibitory effect of gemfibrozil on the invasion of T-bet-positive T cells into the spinal cord of EAE mice. Furthermore, we demonstrate that the differential effect of gemfibrozil on the expression of T-bet and GATA3 was due to its inhibitory effect on NO production. Although excess NO favored the expression of T-bet, scavenging of NO stimulated the expression of GATA-3. Taken together, our results suggest gemfibrozil, an approved drug for hyperlipidemia in humans, may find further therapeutic use in multiple sclerosis.
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|---|---|---|---|---|
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| Amelioration of experimental autoimmune encephalomyelitis by gemfibrozil in mice via PPARΞ²/Ξ΄: implications for multiple sclerosis. | Mondal S et al. | β | 2024 | β |
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| Induction of IL-2 by interleukin-12 p40 homodimer and IL-12, but not IL-23, in microglia and macrophages: Implications for multiple sclerosis. | Jana M et al. | β | 2024 | β |
| Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms. | Ivraghi MS et al. | β | 2024 | β |
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| Autophagy augmentation alleviates cigarette smoke-induced CFTR-dysfunction, ceramide-accumulation and COPD-emphysema pathogenesis. | Bodas M et al. | β | 2019 | β |
| Exploiting the Therapeutic Potential of Endogenous Immunomodulatory Systems in Multiple Sclerosis-Special Focus on the Peroxisome Proliferator-Activated Receptors (PPARs) and the Kynurenines. | Fakan B et al. | β | 2019 | β |
| Oleoylethanolamide treatment reduces neurobehavioral deficits and brain pathology in a mouse model of Gulf War Illness. | Joshi U et al. | β | 2018 | β |
| Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression. | Nikravesh H et al. | β | 2018 | β |
| Antigen presentation for priming T cells in central system. | Dasgupta S et al. | β | 2017 | β |
| Gemfibrozil, food and drug administration-approved lipid-lowering drug, increases longevity in mouse model of late infantile neuronal ceroid lipofuscinosis. | Ghosh A et al. | β | 2017 | β |
| Master Autophagy Regulator Transcription Factor EB Regulates Cigarette Smoke-Induced Autophagy Impairment and Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis. | Bodas M et al. | β | 2017 | β |
| PPARs in the central nervous system: roles in neurodegeneration and neuroinflammation. | Zolezzi JM et al. | β | 2017 | β |
| Unlike PPARgamma, neither other PPARs nor PGC-1alpha is elevated in the cerebrospinal fluid of patients with multiple sclerosis. | Szalardy L et al. | β | 2017 | β |
| Neutralization of RANTES and Eotaxin Prevents the Loss of Dopaminergic Neurons in a Mouse Model of Parkinson Disease. | Chandra G et al. | β | 2016 | β |
| PPARΞ± in lysosomal biogenesis: A perspective. | Ghosh A et al. | β | 2016 | β |
| Activation of peroxisome proliferator-activated receptor Ξ± induces lysosomal biogenesis in brain cells: implications for lysosomal storage disorders. | Ghosh A et al. | β | 2015 | β |
| Attenuation of microglial RANTES by NEMO-binding domain peptide inhibits the infiltration of CD8(+) T cells in the nigra of hemiparkinsonian monkey. | Roy A et al. | β | 2015 | β |
| Cinnamon ameliorates experimental allergic encephalomyelitis in mice via regulatory T cells: implications for multiple sclerosis therapy. | Mondal S et al. | β | 2015 | β |
| "Disease modifying nutricals" for multiple sclerosis. | Schmitz K et al. | β | 2015 | β |
| Gemfibrozil attenuates the inflammatory response and protects rats from abdominal sepsis. | CΓ‘mara-Lemarroy CR et al. | β | 2015 | β |
| Peroxisome proliferator-activated receptors Ξ± and Ξ³ are linked with alcohol consumption in mice and withdrawal and dependence in humans. | Blednov YA et al. | β | 2015 | β |
| Interleukin-12 (IL-12), but not IL-23, induces the expression of IL-7 in microglia and macrophages: implications for multiple sclerosis. | Jana M et al. | β | 2014 | β |
| R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice. | Schmitz K et al. | β | 2014 | β |
| Effects of three different fibrates on intrahepatic cholestasis experimentally induced in rats. | El-Sisi A et al. | β | 2013 | β |
| Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus. | Khalaj L et al. | β | 2013 | β |
| Promoting return of function in multiple sclerosis: An integrated approach. | Gacias M et al. | β | 2013 | β |
| 5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-Ξ³-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability. | Lee JH et al. | β | 2012 | β |
| A role for peroxisome proliferator-activated receptors in the immunopathology of schistosomiasis? | Anthony BJ et al. | β | 2012 | β |
| Crosstalk between Nitric Oxide and T helper cells. | Pahan K et al. | β | 2012 | β |
| Gemfibrozil, a lipid-lowering drug, increases myelin genes in human oligodendrocytes via peroxisome proliferator-activated receptor-Ξ². | Jana M et al. | β | 2012 | β |
| Gemfibrozil, a lipid-lowering drug, induces suppressor of cytokine signaling 3 in glial cells: implications for neurodegenerative disorders. | Ghosh A et al. | β | 2012 | β |
| Gemfibrozil, a lipid lowering drug, inhibits the activation of primary human microglia via peroxisome proliferator-activated receptor Ξ². | Jana M et al. | β | 2012 | β |
| Gemfibrozil, a lipid-lowering drug, upregulates IL-1 receptor antagonist in mouse cortical neurons: implications for neuronal self-defense. | Corbett GT et al. | β | 2012 | β |
| Gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, up-regulate tripeptidyl-peptidase 1 in brain cells via peroxisome proliferator-activated receptor Ξ±: implications for late infantile Batten disease therapy. | Ghosh A et al. | β | 2012 | β |
| PPARΞ± as a therapeutic target in inflammation-associated diseases. | Gervois P et al. | β | 2012 | β |
| Protection of Tregs, suppression of Th1 and Th17 cells, and amelioration of experimental allergic encephalomyelitis by a physically-modified saline. | Mondal S et al. | β | 2012 | β |
| Immunomodulation of experimental allergic encephalomyelitis by cinnamon metabolite sodium benzoate. | Pahan K | β | 2011 | β |
| Peroxisome proliferator-activated receptor-Ξ± agonists protect cortical neurons from inflammatory mediators and improve peroxisomal function. | Gray E et al. | β | 2011 | β |
| PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. | Varga T et al. | β | 2011 | β |
| Regulation of type 17 helper T-cell function by nitric oxide during inflammation. | Niedbala W et al. | β | 2011 | β |
| The PPAR alpha agonist gemfibrozil is an ineffective treatment for spinal cord injured mice. | Almad A et al. | β | 2011 | β |
| Myelin basic protein priming reduces the expression of Foxp3 in T cells via nitric oxide. | Brahmachari S et al. | β | 2010 | β |
| Peroxisome proliferator-activated receptor (PPAR): balance for survival in parasitic infections. | Chan MM et al. | β | 2010 | β |
| Regulation of Immune Responses and Autoimmune Encephalomyelitis by PPARs. | Yang Y et al. | β | 2010 | β |
| Regulation of oligodendrocyte progenitor cell maturation by PPARΞ΄: effects on bone morphogenetic proteins. | Vittoria Simonini M et al. | β | 2010 | β |
| Role of PPARs in Radiation-Induced Brain Injury. | Ramanan S et al. | β | 2010 | β |
| Docosahexaenoic acid modulates the expression of T-bet and GATA-3 transcription factors, independently of PPARalpha, through suppression of MAP kinase activation. | Attakpa E et al. | β | 2009 | β |
| Functional blocking monoclonal antibodies against IL-12p40 homodimer inhibit adoptive transfer of experimental allergic encephalomyelitis. | Mondal S et al. | β | 2009 | β |
| Gemfibrozil, stretching arms beyond lipid lowering. | Roy A et al. | β | 2009 | β |
| Inhibition of calpain attenuates encephalitogenicity of MBP-specific T cells. | Guyton MK et al. | β | 2009 | β |
| Peroxisome proliferator-activated receptor-gamma agonists promote differentiation and antioxidant defenses of oligodendrocyte progenitor cells. | Bernardo A et al. | β | 2009 | β |
| Suppression of regulatory T cells by IL-12p40 homodimer via nitric oxide. | Brahmachari S et al. | β | 2009 | β |
| Transcriptional modulation of the immune response by peroxisome proliferator-activated receptor-{alpha} agonists in autoimmune disease. | Gocke AR et al. | β | 2009 | β |
| PPAR Action in Human Placental Development and Pregnancy and Its Complications. | Wieser F et al. | β | 2008 | β |
| PPAR Alpha Regulation of the Immune Response and Autoimmune Encephalomyelitis. | Yang Y et al. | β | 2008 | β |
| PPAR-gamma, Microglial Cells, and Ocular Inflammation: New Venues for Potential Therapeutic Approaches. | Malchiodi-Albedi F et al. | β | 2008 | β |
| PPAR Regulation of Inflammatory Signaling in CNS Diseases. | Bright JJ et al. | β | 2008 | β |
| RAR/RXR and PPAR/RXR signaling in neurological and psychiatric diseases. | van Neerven S et al. | β | 2008 | β |
| Regulation of Glial Cell Functions by PPAR-gamma Natural and Synthetic Agonists. | Bernardo A et al. | β | 2008 | β |
| Targeting PPAR as a therapy to treat multiple sclerosis. | Bright JJ et al. | β | 2008 | β |
| The peroxisome: still a mysterious organelle. | Schrader M et al. | β | 2008 | β |