Author(s): Jiang CY, Wang W, Tang JX, Yuan ZR
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Abstract 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-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. RESULTS: 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). CONCLUSIONS: 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.
This article was published in J Endocrinol Invest
and referenced in Endocrinology & Metabolic Syndrome