Proinflammatory cytokines differentially regulate hyaluronan synthase isoforms in fetal and adult fibroblasts.
OBJECTIVE
Fetal wound healing is a relatively scarless process that occurs in an hyaluronan-rich environment. Understanding the regulation of hyaluronan expression may provide insight into the process of fetal repair. Therefore, the purpose of this study was to compare the regulation of hyaluronan and hyaluronan synthase transcripts by the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in human adult and fetal fibroblasts.


METHODS
Hyaluronan deposited in the medium of untreated fibroblasts or fibroblasts treated with either IL-1beta or TNF-alpha was determined by an assay utilizing iodine I 125-hyaluronan binding protein. HAS transcript levels were compared in using a ribonuclease protection assay.


RESULTS
IL-1beta induced an increase in hyaluronan accumulation by both fetal and adult fibroblasts. In contrast, TNF-alpha induced higher levels of hyaluronan only in fetal fibroblasts. HAS-2 and HAS-3 transcript levels were constitutively expressed by both fetal and adult fibroblasts. Proinflammatory cytokines induced a differential increase in HAS-1 and HAS-3 transcript levels.


CONCLUSIONS
Differential regulation was observed in hyaluronan accumulation and for HAS transcript levels in fetal and adult dermal fibroblasts. The muted response of fetal fibroblasts to cytokines may be relevant to the minimal inflammation associated with fetal repair.
Kennedy
C I
CI
Department of Surgery, Medical College of Virginia Hospitals, Virginia Commonwealth University, Richmond, USA.
Diegelmann
R F
RF
Haynes
J H
JH
Yager
D R
DR
D000328:Adult; D002478:Cells, Cultured; D005333:Fetus / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology*; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D018836:Inflammation Mediators / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D008565:Membrane Proteins; D012867:Skin / Q000166:cytology; D014166:Transferases; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D029867:Xenopus Proteins
D018836:Inflammation Mediators; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D029867:Xenopus Proteins; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases