科研之友
微信
新浪微博
Facebook
分享链接
摘要
Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin (R) (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive. We hypothesize that NTP functions to suppress inflammatory pathways, thereby attenuating disease progression. In the present study, we investigated whether NTP suppresses inflammatory signaling and cell death pathways induced by interleukin-1 beta (IL-1b) and tumor necrosis factor-alpha (TNF alpha) in hepatocytes. NTP suppressed nuclear factor-kappa B (NF-kappa B) activation induced by IL-1 beta and TNF alpha assessed by using hepatocytes isolated from NF-kappa B-green fluorescent protein (GFP) reporter mice and an NF-kappa B-luciferase reporter system. The expression of NF-kappa B target genes, II6, Nos2, Cxcl1, ccl5 and Cxcl2 induced by IL-1 beta and TNF alpha was suppressed after NTP treatment. We also found that NTP suppressed the JNK phosphorylation induced by IL-1 beta and TNF alpha. Because JNK activation contributes to hepatocyte death, we determined that NTP treatment suppressed hepatocyte death induced by IL-1 beta and TNF alpha in combination with actinomycin D. Taken together, our data demonstrate that NTP attenuates IL-1 beta and TNF alpha-mediated inflammatory cytokine expression and cell death in hepatocytes through the suppression of NF-kappa B and JNK. The results from the present study suggest that NTP may become a preventive or therapeutic strategy for alcoholic and non-alcoholic fatty liver disease in which NF-kappa B and JNK are thought to take part.
- 出版日期2014-12-3
