Proinflammatory cytokines regulate the gene expression of hyaluronic acid synthetase in cultured rabbit synovial membrane cells.
To elucidate the mechanism of accumulation and fragmentation of hyaluronic acid (HA) under inflammatory conditions, we investigated the effect of proinflammatory cytokines on hyaluronic acid synthetase (HAS) mRNA expression using cultured rabbit synovial membrane cells. HASs mRNA levels were determined by real-time PCR. HAS2 mRNA expression was maximally enhanced 3.3- and 2.8-fold after 3-hour stimulation with IL-1beta (1 ng/ml) and after 1-hour stimulation with TNF-alpha (10 ng/ml). HAS3 mRNA expression was increased by a maximum of 4.3 times after 3-hour stimulation with IL-1beta (10 ng/ml), whereas 1-hour stimulation with TNF-alpha (10 ng/ml) and IFN-gamma (10 ng/ml) induced around a 2.5-fold increase in HAS3 mRNA. Although IFN-gamma (1-100 ng/ml) alone showed little effect on HAS2 mRNA expression, the effect was synergized by combined with both IL-1beta and TNF-alpha, substantially increasing HAS2 mRNA expression. These results suggest that proinflammatory cytokines regulate the HAS expression, and consequently may contribute to the accumulation and fragmentation of HA.
Tanimoto
K
K
Department of Orthodontics and Biochemistry, Hiroshima University, Faculty of Dentistry, Kasumi, Japan. tkotaro@hiroshima-u.ac.jp
Ohno
S
S
Fujimoto
K
K
Honda
K
K
Ijuin
C
C
Tanaka
N
N
Doi
T
T
Nakahara
M
M
Tanne
K
K
D000818:Animals; D001168:Arthritis / Q000201:enzymology* / Q000503:physiopathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000235:genetics*; D016695:Glycosyltransferases; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D014166:Transferases; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D029867:Xenopus Proteins
D016207:Cytokines; D004338:Drug Combinations; D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D029867:Xenopus Proteins; D007371:Interferon-gamma; D006820:Hyaluronic Acid; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases