Induction of leukemia inhibitory factor in human synovial fibroblasts by IL-1 and tumor necrosis factor-alpha.
The cytokines, IL-1 alpha and TNF-alpha, induced a dose-dependent production of leukemia inhibitory factor (LIF) in cultured human synovial fibroblast-like cells, as measured by a radioreceptor competition assay. Significant levels of LIF were first detected in cell supernatants between 2 and 4 h after cytokine addition. Increases were also observed in LIF mRNA steady-state expression. Evidence is presented for down-regulation of the IL-1-induced LIF activity by an endogenous cyclo-oxygenase product(s); the glucocorticoid, dexamethasone, lowered the IL-1-induced LIF activity and mRNA expression. A synergistic effect was noted between the actions of IL-1 alpha and TNF-alpha, and between IL-1 and transforming growth factor-beta. IFN-gamma could not induce LIF formation in the synovial cells but inhibited the stimulatory effect of IL-1. These results suggest that cytokine-stimulated synovial fibroblasts may be a major source of intraarticular LIF production in the joints of patients with inflammatory arthritis. Synoviocyte-derived LIF may activate monocyte/macrophages in the lesions and may contribute to the bone changes and certain systemic manifestations in patients with inflammatory joint disease.
Hamilton
J A
JA
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Waring
P M
PM
Filonzi
E L
EL
D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011869:Radioligand Assay; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016207:Cytokines; D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin