Hyaluronan in human acute and chronic dermal wounds.

There is growing interest in the relationship of hyaluronan and inflammation in a number of physiologic processes including wound healing. The objective of this study was to make a quantitative comparison of inflammation and hyaluronan expression in human normal healing open wounds and in pressure ulcers. Using an open dermal wound model, myeloperoxidase activity was found to peak at day 3. Hyaluronan levels showed a bimodal distribution with transient peaks occurring on days 1 and 7. Mean levels of myeloperoxidase activity in pressure ulcers were significantly higher than at any time in the acute wounds, whereas hyaluronan levels were significantly lower than at any time in the acute wounds. Levels of hyaluronidase activity increased slightly in the postwound period. Hyaluronidase activity in pressure ulcers was significantly elevated compared with the acute wounds. These results suggest a role for increased enzymatic degradation of hyaluronan as a function of inflammation during wound repair. This is the first reported quantitative examination of hyaluronan expression in human acute dermal wounds and in chronic pressure ulcers.

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

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-1beta, TNF-alpha, IFN-gamma, or transforming growth factor-beta (TGF-beta) and hyaluronan expression in human JDMC and, if so, to identify possible mechanisms involved in the induction of hyaluronan expression. TGF-beta, TNF-alpha, and IFN-gamma had little or no effect on hyaluronan production by these cells. Treatment with IL-1beta 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-1beta. HAS3 transcript levels were also increased slightly by exposure of these cells to IL-1beta. Expression of HAS1 transcripts was not detected under any condition in these cells. IL-1beta 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-1beta-mediated induction of hyaluronan expression and the increase in HAS2 transcript expression. These results suggest that IL-1beta 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.