Suppression of IL-6 biological activities by activin A and implications for inflammatory arthropathies.
Activin A is a cytokine whose multiple functions have yet to be fully determined. In this study, the role of proinflammatory cytokines in regulatory control of activin A production was shown in synoviocytes and chondrocytes. Additional facets of functional inflammation-related activities of activin A were also determined. Results showed that activin A concentrations in the synovial fluid of patients with rheumatoid arthritis and gout were elevated relative to those in patients with osteoarthritis. Further studies showed that production of activin A by synoviocytes and chondrocytes in culture was stimulated by cytokines such as IL-1, transforming growth factor-beta (TGF-beta), interferon-gamma (IFN-gamma), and IL-8, consistent with previous studies in regard to the control of activin A production in marrow stromal cells and monocytes by cytokines, glucocorticoids and retinoic acid. In addition, the relationship of activin A to IL-6-induced biological activities was investigated. Three major IL-6 activities involved in inflammatory responses were found to be suppressed by activin A. In a dose-dependent manner, activin A efficiently suppressed IL-6-induced proliferation of 7TD1 B lymphoid cells, phagocytic activity of monocytic M1 cells, and fibrinogen production in HepG2. Therefore, it is likely that activin A serves as a suppressor for IL-6, dampening inflammatory responses, and has the potential to perform some previously unrecognized roles in inflammation.
Yu
E W
EW
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Dolter
K E
KE
Shao
L E
LE
Yu
J
J
D028341:Activins; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D019902:Chondrocytes / Q000276:immunology*; D006801:Humans; D007265:Inhibins / Q000276:immunology* / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D010003:Osteoarthritis / Q000276:immunology* / Q000378:metabolism; D013582:Synovial Fluid / Q000276:immunology*; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D007371:Interferon-gamma