Hyaluronan production in human rheumatoid fibroblastic synovial lining cells is increased by interleukin 1 beta but inhibited by transforming growth factor beta 1.
OBJECTIVE
To investigate the regulatory roles of interleukin 1 beta (IL1 beta), tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or transforming growth factor beta 1 (TGF beta 1) on hyaluronan (HA) synthesis by human fibroblastic synovial lining cells.


METHODS
Concentrations of HA in culture supernatants of fibroblastic synovial lining cell line (RAMAK-1 cell line) with or without stimulation by IL1 beta, TNF alpha, IFN gamma or TGF beta 1 were measured by sandwich binding protein assay. Levels of HA synthase mRNA of the cells with or without stimulation were detected by reverse transcribed polymerase chain reaction. Molecular weights of HA in the culture supernatants of the cells with or without stimulation were measured using high performance gel permeation liquid chromatography.


RESULTS
HA synthesis by the cells was not significantly augmented by TNF alpha or by IFN gamma. It was significantly stimulated by IL1 beta but inhibited by TGF beta 1. Molecular weights of HA in the culture supernatants of the cells were unchanged by stimulation with TNF alpha. They were remarkably increased by stimulation with IL1 beta and IFN gamma, but reduced with TGF beta 1.


CONCLUSIONS
IL 1 beta is an up regulator of HA synthesis, while TGF beta 1 is a down regulator. HA production in the synovial lining cells of inflamed joints (for example, rheumatoid arthritis) might be regulated by the balance of these cytokines.
Kawakami
M
M
National Defence Medical College, Saitama, Japan.
Suzuki
K
K
Matsuki
Y
Y
Ishizuka
T
T
Hidaka
T
T
Konishi
T
T
Matsumoto
M
M
Kataharada
K
K
Nakamura
H
H
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D018929:Cell Culture Techniques; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000737:chemistry; D007375:Interleukin-1 / Q000494:pharmacology; D008565:Membrane Proteins; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism*; D014166:Transferases; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D029867:Xenopus Proteins
D016207:Cytokines; D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D006820:Hyaluronic Acid; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases