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

Abstract

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. 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. 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-α) 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-κB p65 subunit protein level was measured by western blotting. Significantly increased amylase secretion and LDH release was observed in the 100 ng/ml resistin treatment (p<0.01). Both TNF-α 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-κB inhibitor PDTC, which decreases the NF-κB p65 subunit protein expression levels in the nuclei, produced significantly lower mRNA expression levels for both TNF-α and IL-6 compared with those produced by resistin-treated cells (p<0.01). Resistin exhibits some cytotoxic activity in rat pancreatic acinar AR42J cells and stimulates proinflammatory cytokine TNF-α and IL-6 production via NF-κB activation. Thus, overproduction of obesity-related circulating resistin and associated lowgrade inflammation may result in mild injury to pancreatic acini, increasing AP severity and risk.