Cytokine-mediated control of lipopolysaccharide-induced activation of small intestinal epithelial cells

Cytokines with anti-inflammatory properties have been implicated in the prevention of inappropriate immune activation by commensal bacteria in the intestinal tract. Here, we analysed receptor expression, cellular signalling, and the inhibitory activity of interleukin (IL)-4, -10, -11, and -13 as well as of transforming growth factor-beta on lipopolysaccharide-mediated small intestinal epithelial cell activation. Only IL-4 and IL-13 had a significant inhibitory effect on chemokine secretion and nitric oxide (NO) production in differentiated and polarized cells. Reverse transcription-polymerase chain reaction of primary intestinal epithelial cells obtained by laser-microdissection confirmed expression of the type II IL-4 receptor consisting of the IL-4 receptor alpha and the IL-13 receptor alpha1. Also, IL-4 or IL-13 led to rapid signal transducer and activator of transcription 6 phosphorylation, diminished inducible NO synthase expression, and enhanced the antagonistic arginase 1 activity. In conclusion, cytokines such as IL-4 and IL-13 affect intestinal epithelial cells and exhibit a modulating activity on Toll-like receptor-4-mediated epithelial cell activation.