Author/Editor		Sodin-Šemrl, S; Spagnolo, A; Barbaro, B; Varga, J; Fiore, S
Title		Lipoxin A4 counteracts synergistic activation of human fibroblast-like synoviocytes
Type		članek
Source		Int J Immunopath Ph
Vol. and No.		Letnik 17, št. 1
Publication year		2004
Volume		str. 15-25
Language		eng
Abstract		Excessive production of interleukin-6 (IL-6) and metalloproteinases (MMPs) has been implicated in the pathogenesis of rheumatoid arthritis. hipoxin A4 (LXA4) and transforming growth factor ß2 (TGF-ß2) have potential anti-inflammatory activities; these two mediators were tested to determine how they affect IL-1(3-dependent release of IL-6 and MMPs in human fibroblast-like synoviocytes. The results revealed dramatic differences between the mediators: TGF-ß2 acted synergistically with IL-1(3 to stimulate IL-6 protein levels, whereas LXAa inhibited IL-6 expression in a dose- and time-dependent manner. Inhibition, by LXA4 was abrogated when cells were pre-incubated with antibody against the ALXR (Lipoxin A4 Receptor) TGF-ß2 by itself had no significant effect on IL-6 or MMP levels. LXA4, at nanomolar concentrations, altered the MMP-1 and MMP-3 expression levels of IL-1ß and TGF-ß2 stimulated fibroblast-like synoviocytes. Furthermore, IL-1ß and TGF-ß2 up-regulated ALXR mRNA. These results demonstrate, for the first time, that ALXR mediate the effects of LXA; on inflammatory responses after stimulation of fibroblast-like synoviocytes with IL-1ß plus TGF-ß2. These activities might constitute an important mechanism by which LXA4 regulates synovial fibroblast activation.
Descriptors		FIBROBLASTS SYNOVIAL FLUID INTERLEUKIN-1 INTERLEUKIN-6 METALLOPROTEINASES CELLS, CULTURED DOSE-RESPONSE RELATIONSHIP, DRUG TRANSFORMING GROWTH FACTOR BETA TIME FACTORS