The adipocytokine resistin stimulates the production of proinflammatory cytokines TNF-α and IL-6 in pancreatic acinar cells via NF-κB activation

Background: Resistin, an adipocytokine secreted by fat tissues, has been associated with the inflammatory response, though its role in inflammation during acute pancreatitis (AP) remains unclear. Objective: The proinflammatory response following acinar cell injury impacts pancreatitis severity, necessitating better understanding of functional consequences associated with pancreatic acinar cell resistin exposure and resultant effects on proinflammatory signaling. Methods: Amylase-secreting rat pancreatic acinar AR42J cells were subjected to 1, 10, or 100 ng/ml recombinant rat resistin treatments. Cytotoxicity was evaluated by amylase secretion and lactate dehydrogenase (LDH) release. Tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) mRNA and protein expressions were determined by real-time real time-PCR and enzyme-linked immunosorbent assay, respectively. Nuclear NF-kappa B p65 subunit protein level was measured by western blotting. Results: Significantly increased amylase secretion and LDH release was observed in the 100 ng/ml resistin treatment (p < 0.01). Both TNF-alpha and IL-6 protein expression levels increased in a concentration-dependent manner when treated with resistin. Pretreatment of resistin- treated AR42J cells with the NF-kappa B inhibitor PDTC, which decreases the NF-kappa B p65 subunit protein expression levels in the nuclei, produced significantly lower mRNA expression levels for both TNF-alpha and IL-6 compared with those produced by resistin-treated cells (p < 0.01). Conclusions: Resistin exhibits some cytotoxic activity in rat pancreatic acinar AR42J cells and stimulates proinflammatory cytokine TNF-alpha and IL-6 production via NF-kappa B activation. Thus, overproduction of obesity-related circulating resistin and associated low-grade inflammation may result in mild injury to pancreatic acini, increasing AP severity and risk. (C) 2013, Editrice Kurtis