Expression of interleukin 10 mRNA and protein by synovial fibroblastoid cells.
OBJECTIVE
To determine if fibroblast-like synoviocytes (FLS) express interleukin 10 (IL-10) mRNA and protein and functional IL-10 receptors.


METHODS
The pattern of IL-10 production was analyzed in inflammatory synovial tissues by immunohistochemistry. Expression of IL-10 mRNA and protein was determined by Northern blot analysis and ELISA in resting FLS and following stimulation with IL-1beta and tumor necrosis factor-alpha (TNF-alpha). IL-10 receptor expression was measured on cultured FLS by immunohistochemistry and FACS analysis after treatment with biotinylated IL-10. Responsiveness of FLS to IL-10 was determined by multigene assay and inhibition of prostaglandin E2 induced morphologic changes. Bioactivity was confirmed by downregulation of interferon-gamma stimulated HLA-DR expression by FACS and inhibition of TNF-alpha production by U937 cells.


RESULTS
Using immunohistochemistry, we detected IL-10 in the lining layer of inflamed synovial tissue and FLS. ELISA on unstimulated third passage FLS culture supernatants revealed IL-10 production that varied over time and among cell lines. FLS produced IL-10 mRNA constitutively. IL-10 production was upregulated by IL-1beta and TNF-alpha. IL-10 bound to receptors on FLS and induced functional changes. Endogenously released FLS IL-10 was biologically active.


CONCLUSIONS
Mesenchymal lining cells in the inflamed joint produce IL-10. In addition, cultured FLS constitutively produce IL-10 mRNA and protein that is bioactive and can be upregulated by IL-1beta and TNF-alpha. FLS express functional IL-10 receptors. These results suggest that IL-10 released by mesenchymal cells in inflammatory arthritis can modulate synovial inflammation and joint destruction by paracrine and/or autocrine mechanisms.
Ritchlin
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C
Clinical Immunology Rheumatology Unit, University of Rochester School of Medicine and Dentistry, New York 14642, USA. christopher_ritchlin@urmc.rochester.edu
Haas-Smith
S A
SA
D015535:Arthritis, Psoriatic / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D013585:Synovitis / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10