Resistin aggravates the expression of proinflammatory cytokines in cerulein­stimulated AR42J pancreatic acinar cells.

Resistin, an adipocytokine secreted by fat tissues, has been shown to be associated with increased local and systemic complications in acute pancreatitis (AP). However, the mechanism underlying the effect of resistin in the aggravation of AP remains to be elucidated. The aim of the present study was to investigate the functional consequences of exposing rat pancreatic acinar cells to resistin and to determine whether it amplifies proinflammatory signaling in an in vitro AP model. AR42J cells pretreated with recombinant resistin were activated by cerulein as an in vitro model of AP. The secretion of amylase was measured to evaluate the cytotoxic effect. The mRNA expression levels of tumor necrosis factor (TNF)­α and interleukin (IL)­6 were determined using reverse transcription­quantitative polymerase chain reaction analysis. The nuclear protein expression levels of the nuclear factor (NF)­κB p65 subunit were determined using western blot analysis. Resistin treatment significantly increased the secretion of amylase, and the mRNA expression levels of TNF­α and IL­6 in the cerulein­induced in vitro AP model. High protein levels of the NF­κB p65 subunit were observed in the nuclei of cells in the resistin­treated AP model, compared with the untreated AP model. Pretreatment of the in vitro resistin­treated AP model with the NF­κB inhibitor, pyrrolidine dithiocarbamate decreased the protein expression of the NF­κB p65 subunit in nuclei, and significantly attenuated the increased mRNA expression levels of TNF­α and IL­6 induced by resistin. The results of the present study showed that resistin increased the production of the TNF­α and IL­6 proinflammatory cytokines via the NF­κB­dependent pathway during AP. Thus, the overproduction of obesity­associated resistin and the associated amplification of the inflammatory response may result in the aggravation of AP severity.