Butyrate and the cytokine-induced alpha1-proteinase inhibitor release in intestinal epithelial cells.

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Alpha1-proteinase inhibitor (alpha1-PI), an anti-inflammatory protein thought to play a role in the intestinal inflammation, is synthesised by and released from the intestinal epithelial cells. IL-1beta is a key proinflammatory cytokine in the abnormal immune response that occurs in inflammatory bowel disease. Butyrate is a normal luminal constituent in the colon, known to be of benefit in preventing inflammatory bowel disease. Direct modes of action of butyrate in intestinal inflammation have been poorly studied so far. The aim of this study was to investigate the effects of butyrate on cytokine-mediated alpha1-PI release in intestinal epithelial cells. Differentiated Caco-2 cells were incubated with IL-1beta in the presence or absence of 2 mM butyrate. Alpha1-PI expression in the cells was evaluated by Western blot analysis and alpha1-PI release by ELISA. Treatment with butyrate alone had no effect on alpha1-PI expression in differentiated Caco-2 cells. However, treatment of the cells with 2 mM butyrate significantly reduced the alpha1-PI level in IL-1beta-treated cells. In the cell culture medium, the presence of butyrate impaired the IL-1beta-induced alpha1-PI release to 17-35%. The treatment induced no change in the number of detached cells or the percentage of viable cells. Our data show that butyrate inhibits alpha1-PI release from Caco-2 colonocytes treated with IL-1beta. It is therefore likely that anti-inflammatory actions of butyrate occur via a mechanism that does not involve direct regulation of cytokine-induced anti-inflammatory protein expression in intestinal epithelial cells.