Expression of the interleukin 6 gene in rheumatoid synovial fibroblasts.
A number of fibroblastoid synovial cell lines have been established from rheumatoid joints. These cell lines were shown to express the interleukin 6 (IL-6) gene constitutively, and exposure of these cells to 5 ng/ml of recombinant human interleukin 1 beta (IL-1 beta) increased IL-6 gene expression. Other recombinant human lymphokines, namely interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor had no enhancing effect on IL-6 gene expression. Dexamethasone added to the cultures at 10(-7) M concentration suppressed the constitutive expression of the IL-6 gene. At a concentration of 10(-5) M, dexamethasone partially suppressed the IL-1 enhanced expression of IL-6. The IL-6 gene probe also hybridized to RNA from unfractionated synovial fluid cells, peripheral blood T cells and non-T cells but not Epstein-Barr virus transformed peripheral blood B cells of patients with rheumatoid arthritis. Our results suggest that in rheumatoid arthritis, synovial fibroblasts actively participate in joint inflammation by lymphokine production. The coexpression of both IL-1 and IL-6 by one synovial fibroblast line suggests a mechanism for the perpetuation of synovitis.
Tan
P L
PL
Department of Molecular Medicine, University of Auckland, New Zealand.
Farmiloe
S
S
Yeoman
S
S
Watson
J D
JD
D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D012313:RNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D013585:Synovitis / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D015850:Interleukin-6; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D003907:Dexamethasone; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor