Jing Qi
Chonbuk National University, South Korea
Title: Nicotine attenuates concanavalin A-induced hepatic injury by regulating Kupffer cells in mice
Biography
Biography: Jing Qi
Abstract
Nicotine, a major constituent of cigarette smoke, is a potent parasympathomimetic alkaloid found in the nightshade family of plants. Acute liver failure (ALF), known as a rapid and severe clinical syndrome, can induce multiple organ dysfunction and failure. This study aimed to investigate the effects of nicotine on concanavalin A (Con A)-induced autoimmune hepatitis in mice and to elucidate its underlying molecular mechanisms. Autoimmune hepatitis was induced by the intravenous administration of Con A (15 mg/kg) to healthy BALB/c male mice, and nicotine (0.5mg/kg and 1mg/kg) was intraperitoneally injected before the challenge with Con A. Eight hours later the mice were euthanized and blood and tissues were collected for analysis. The present study showed that nicotine pretreatment significantly decreased the elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and ameliorated hepatic pathological damage and necrosis. In addition, nicotine treatment markedly suppressed the secretion of pro-inflammatory cytokines and chemokines including tumor necrosis factor-a (TNF-a), interferon (IFN)-γ, and interleukin (IL)-4. Furthermore, nicotine down-regulated the activation of NF-kB signal in Con A-treated mouse livers. Since Kupffer cells have been known as a crucial component in the initial part of pathogenesis of ALF, our present study confirmed that depletion of Kupffer cells by liposomal clodronate abolished the protective effects of nicotine against ConA-induced hepatitis, as shown by the similar levels of serum aminotransferase levels and pro-inflammatory cytokines with or without nicotine treatment in Con A-treated mouse livers. In the primary Kupffer cells, nicotine ameliorated inflammatory cytokines and regulated the expression of NF-kB signal. Consistent with the above findings, this study suggested that nicotine could attenuate Con A-induced autoimmune hepatitis and possible mechanism might be associated with the inhibition of Kupffer cells activation through NF-kB signal pathway.