Neurotropin suppresses inflammatory cytokine expression and cell death through suppression of NF-κB and JNK in hepatocytes

Bi Zhang, Yoon Seok Roh, Shuang Liang, Cheng Liu, Mitsuru Naiki, Koichi Masuda, Ekihiro Seki

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (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-1β (IL-1β) and tumor necrosis factor-α (TNFα) in hepatocytes. NTP suppressed nuclear factor-κB (NF-κB) activation induced by IL-1β and TNFα assessed by using hepatocytes isolated from NF-κB-green fluorescent protein (GFP) reporter mice and an NF-κB-luciferase reporter system. The expression of NF-κB target genes, Il6, Nos2, Cxcl1, ccl5 and Cxcl2 induced by IL-1β and TNFα was suppressed after NTP treatment. We also found that NTP suppressed the JNK phosphorylation induced by IL-1β and TNFα. Because JNK activation contributes to hepatocyte death, we determined that NTP treatment suppressed hepatocyte death induced by IL-1b and TNFa in combination with actinomycin D. Taken together, our data demonstrate that NTP attenuates IL-1β and TNFα-mediated inflammatory cytokine expression and cell death in hepatocytes through the suppression of NF-κB 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-κB and JNK are thought to take part.

Original languageEnglish (US)
Article numbere114071
JournalPloS one
Volume9
Issue number12
DOIs
StatePublished - Dec 3 2014
Externally publishedYes

Fingerprint

Cell death
tumor necrosis factors
interleukin-1
hepatocytes
cell death
Hepatocytes
Cell Death
cytokines
Cytokines
Interleukin-1
pain
Tumor Necrosis Factor-alpha
death
therapeutics
actinomycin D
fatty liver
liver diseases
luciferase
alcohol abuse
Chronic Pain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Neurotropin suppresses inflammatory cytokine expression and cell death through suppression of NF-κB and JNK in hepatocytes. / Zhang, Bi; Roh, Yoon Seok; Liang, Shuang; Liu, Cheng; Naiki, Mitsuru; Masuda, Koichi; Seki, Ekihiro.

In: PloS one, Vol. 9, No. 12, e114071, 03.12.2014.

Research output: Contribution to journalArticle

Zhang, Bi ; Roh, Yoon Seok ; Liang, Shuang ; Liu, Cheng ; Naiki, Mitsuru ; Masuda, Koichi ; Seki, Ekihiro. / Neurotropin suppresses inflammatory cytokine expression and cell death through suppression of NF-κB and JNK in hepatocytes. In: PloS one. 2014 ; Vol. 9, No. 12.
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