Proinflammatory cytokines differentially regulate hyaluronan synthase isoforms in fetal and adult fibroblasts

Background/Purpose: Fetal wound healing is a relatively scarless process th at occurs in an hyaluronan-rich environment. Understanding the regulation o f hyaluronan expression may provide insight into the process of fetal repai r. Therefore, the purpose of this study was to compare the regulation of hy aluronan and hyaluronan synthase transcripts by the proinflammatory cytokin es interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alph a) in human adult and fetal fibroblasts. Methods: Hyaluronan deposited in the medium of untreated fibroblasts or fib roblasts treated with either IL-1 beta or TNF-alpha was determined by an as say utilizing iodine I 125-hyaluronan binding protein. HAS transcript level s were compared in using a ribonuclease protection assay. Results: IL-1 beta induced an increase in hyaluronan accumulation by both f etal and adult fibroblasts. in contrast, TNF-alpha induced higher levels of hyaluronan only in fetal fibroblasts. HAS-2 and HAS-3 transcript levels we re constitutively expressed by both fetal and adult fibroblasts. Proinflamm atory cytokines induced a differential increase in HAS-1 and HAS-3 transcri pt levels. Conclusions: Differential regulation was observed in hyaluronan accumulatio n and for HAS transcript levels in fetal and adult dermal fibroblasts. The muted response of fetal fibroblasts to cytokines may be relevant to the min imal inflammation associated with fetal repair. Copyright (C) 2000 by W.B. Saunders Company.