title: The adipocytokine resistin stimulates the production of proinflammatory cytokines TNF-α and IL-6 in pancreatic acinar cells via NF-κB activation.
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.
authors.affiliation: Department of General Surgery, Huadong Hospital Affiliated To Fudan University, Shanghai 200040, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Jiang
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: J X
authors.initials: JX
authors.lastname: Tang
authors.forename: Z R
authors.initials: ZR
authors.lastname: Yuan
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000378:metabolism*; D000681:Amylases / Q000378:metabolism; D000818:Animals; D015850:Interleukin-6 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000502:physiology*; D010195:Pancreatitis / Q000503:physiopathology; D051381:Rats; D052243:Resistin / Q000494:pharmacology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D052243:Resistin; C499622:Retn protein, rat; D014409:Tumor Necrosis Factor-alpha; D000681:Amylases