title: Acetaldehyde-induced interleukin-1beta and tumor necrosis factor-alpha production is inhibited by berberine through nuclear factor-kappaB signaling pathway in HepG2 cells.
abstract: Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Increased levels of proinflammatory cytokines, including interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), have been correlated with the patients affected by ALD. However, the direct effect of alcohol in the induction of IL-1beta and TNF-alpha has not been clarified. In this study, we demonstrated that acetaldehyde, the metabolic product of ethanol, was able to induce IL-1beta and TNF-alpha production in HepG2 cells. Nuclear factor-kappaB (NF-kappaB), the transcription factor involved in the regulation of cytokine production, was also activated by acetaldehyde through inhibitory kappaB-alpha (IkappaB-alpha) phosphorylation and degradation. However, the NF-kappaB inhibitors, such as aspirin, cyclosporin A and dexamethasone, inhibited both the acetaldehyde-induced NF-kappaB activity and the induced cytokine production. Therefore, these data suggested that acetaldehyde stimulated IL-1beta and TNF-alpha production via the regulation of NF-kappaB signaling pathway. By screening 297 controlled Chinese medicinal herbs supervised by Committee on Chinese Medicine and Pharmacy at Taiwan, we found that Coptis chinensis (Huang-Lien) and Phellodendron amurense (Huang-Po) were capable of inhibiting acetaldehyde-induced NF-kappaB activity. Berberine, the major ingredient of these herbs, abolished acetaldehyde-induced NF-kappaB activity and cytokine production in a dose-dependent manner. Moreover, its inhibitory ability was through the inhibition of induced IkappaB-alpha phosphorylation and degradation. In conclusion, we first linked the acetaldehyde-induced NF-kappaB activity to the induced proinflammatory cytokine production in HepG2 cells. Our findings also suggested the potential role of berberine in the treatment of ALD.
authors.affiliation: Graduate Institute of Medical Science, China Medical University, Taichung 404, Taiwan. cyhsiang@mail.cmu.edu.tw
authors.forename: Chien-Yun
authors.initials: CY
authors.lastname: Hsiang
authors.forename: Shih-Lu
authors.initials: SL
authors.lastname: Wu
authors.forename: Shin-Ei
authors.initials: SE
authors.lastname: Cheng
authors.forename: Tin-Yun
authors.initials: TY
authors.lastname: Ho
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D000079:Acetaldehyde