Regulation of hyaluronan synthase-2 expression in human intestinal mesenchymal cells: mechanisms of interleukin-1 -mediated induction

Ducale, Ashley E., Susan I. Ward, Tracey Dechert, and Dorne R. Yager. Regulation of hyaluronan synthase-2 expression in human intestinal mesenchymal cells: mechanisms of interleukin-1 -mediated induction. Am J Physiol Gastrointest Liver Physiol 289: G462–G470, 2005. First published January 27, 2005; doi:10.1152/ajpgi.00494.2004.—Elevated levels of hyaluronan are associated with numerous inflammatory diseases including inflammatory bowel disease. The purpose of this study was to determine whether a cause and effect relationship might exist among proinflammatory cytokines, IL-1 , TNF, IFN, or transforming growth factor(TGF) and hyaluronan expression in human JDMC and, if so, to identify possible mechanisms involved in the induction of hyaluronan expression. TGF, TNF, and IFNhad little or no effect on hyaluronan production by these cells. Treatment with IL-1 induced an approximate 30-fold increase in the levels of hyaluronan in the medium of human jejunum-derived mesenchymal cells. Ribonuclease protection analysis revealed that steady-state transcript levels for hyaluronan synthase (HAS)2 were present at very low levels in untreated cells but increased as much as 18-fold in the presence of IL-1 . HAS3 transcript levels were also increased slightly by exposure of these cells to IL-1 . Expression of HAS1 transcripts was not detected under any condition in these cells. IL-1 induction of hyaluronan expression was inhibited in cells transfected with short interfering RNA corresponding to HAS2 transcripts. Inhibitors of the p38 and ERK1/2 mitogen-activated pathways but not JNK/SAPK blocked the IL-1 -mediated induction of hyaluronan expression and the increase in HAS2 transcript expression. These results suggest that IL-1 induction of HAS2 expression involves multiple signaling pathways that act in concert, thus leading to an increase in expression of hyaluronan by jejunum-derived mesenchymal cells.