Enhanced interleukin-33 expression and mast cell activation in pancreas and lung tissues of pancreatic duct ligation-induced acute pancreatitis in rodents (117.16)

Abstract

Abstract IL-33 is a newly identified member of the IL-1 cytokine family mainly expressed by epithelial cells, endothelial cells, fibroblasts, macrophages and mast cells. IL-33 release is known to increase in tissues of inflammation and is a potent activator of immune cells including mast cells. Elevation of IL-1β and TNF-α in acute pancreatitis has been already reported, and these cytokines upregulate IL-33 expression in inflammation. Activation of mast cells leads to the release of preformed mediators (eg., histamine) and proinflammatory cytokines (eg., IL-1β, TNF-α) and chemokines. Here we investigated mast cell activation and IL-33 expression following 5-48 hr of distal pancreatic duct ligation (PD)-induced acute pancreatitis in rats and mice. PD showed mast cell degranulation in the pancreas and lung, compared to sham controls. Rat plasma showed increased histamine levels with 48 hr of PD than sham controls. Immunohistochemistry, ELISA and immunoblotting results showed increased IL-33 expression in the rat and mouse exocrine pancreas and lung with 5-48 hr of PD. Murine bronchoalveolar lavage fluid showed higher IL-33 level in 48 hr of PD. Mast cell derived mediators and enhanced IL-33 expression may contribute to the progression of pancreatic and pulmonary inflammation. These results will enhance our understanding of acute pancreatitis pathogenesis and could indicate new therapeutic targets.