This suggested that enhanced N-SMase activity is a key part of the mechanism underlying IL-1β hypersensitivity. Consistent with this, it was reported that nSMase2 overexpression in hepatocytes from young rats leads to reduced IRAK-1 degradation and increased JNK phosphorylation whereas the inhibition of N-SMase significantly abrogated the IL-1β response in hepatocytes from aged rats. These important studies demonstrated that nSMase2 is both sufficient and required for the onset of hyperresponsive to IL-1 β during aging (Rutkute et al., 2007b). Moreover, it was also revealed that the observed increase in N-SMase activity during aging was caused by a decrease in hepatocyte GSH level (Rutkute et al., 2007a).
