Somatostatin through its specific receptor inhibits spontaneous and TNF-alpha- and bacteria-induced IL-8 and IL-1 beta secretion from intestinal epithelial cells

Intestinal epithelial cells secrete proinflammatory cytokines and chemokine s that are crucial in mucosal defense. However, this secretion must be tigh tly regulated, because uncontrolled secretion of proinflammatory mediators may lead to chronic inflammation and mucosal damage, The aim of this study was to determine whether somatostatin, secreted within the intestinal mucos e, regulates secretion of cytokines from intestinal epithelial cells. The s pontaneous as well as TNF-alpha- and Salmonella-induced secretion of IL-8 a nd IL-1 beta derived from intestinal cell lines Caco-2 and HT-29 was measur ed after treatment with somatostatin or its synthetic analogue, octreotide. Somatostatin, at physiological nanomolar concentrations, markedly inhibite d the spontaneous and TNF-alpha -induced secretion of IL-8 and IL-1 beta, T his inhibition was dose dependent, reaching >90% blockage at 3 nM, Furtherm ore, somatostatin completely abrogated the increased secretion of IL-8 and IL-1 beta after invasion by Salmonella, Octreotide, which mainly stimulates somatostatin receptor subtypes 2 and 5, affected the secretion of IL-8 and IL-1 beta similarly, and the somatostatin antagonist cyclo-somatostatin co mpletely blocked the somatostatin- and octreotide-induced inhibitory effect s. This inhibition was correlated to a reduction of the mRNA concentrations of IL-8 and IL-1 beta, No effect was noted regarding cell viability, These results indicate that somatostatin, by directly interacting with its speci fic receptors that are expressed on intestinal epithelial cells, down-regul ates proinflammatory mediator secretion by a mechanism involving the regula tion of transcription, These findings suggest that somatostatin plays an ac tive role in regulating the mucosal inflammatory response of intestinal epi thelial cells after physiological and pathophysiological stimulations such as bacterial invasion.