Synoviocytes in chronic synovitis in situ and cytokine stimulated synovial cells in vitro neo-express alpha 1, alpha 3 and alpha 5 chains of beta 1 integrins.
The expression of the beta 1 integrins was examined immunohistochemically in synoviocytes from normal synovitis membrane and from chronic synovitis of different aetiology and intensity. Normal synoviocytes were alpha 6 beta 1-positive but lacked alpha 1 through alpha 5. In mild inflammation type A synoviocytes neo-expressed alpha 1, alpha 3, and alpha 5 chains. In severe inflammation both type A and B synoviocytes expressed alpha 3, alpha 4, alpha 5, and alpha 6 chains. The effects of inflammatory cytokines, as single agents or in combination, on the beta 1 integrin expression in cultured normal synoviocytes was determined by immunocytochemistry and flow cytometry. The alpha 1 chain, while absent in unstimulated synoviocytes, was induced by interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). This effect was enhanced by combining IL-1 beta and TNF-alpha. Expression of the alpha 3 chain was up-regulated by IL-1 beta and, more intensely, by IFN-gamma. Transforming growth factor beta (TGF-beta) inhibited the up-regulating effect of IL-1 beta and antagonized the effect of IFN-gamma on alpha 3 chain expression. Expression of the alpha 5 chain was up-regulated significantly by co-stimulation through IL-1 beta together with TGF-beta or TNF-alpha. Thus, the beta 1 integrin profile of cytokine activated synoviocytes in vitro resembled that of synoviocytes in synovitis in situ. These data suggest that IL-1 beta, TNF-alpha, IFN-gamma, and TGF-beta are likely to be among the effectors regulating beta 1 integrin expression in synoviocytes in vivo.
Rinaldi
N
N
Institute of Pathology, Heidelberg, Germany.
Barth
T
T
Henne
C
C
Mechterscheimer
G
G
Möller
P
P
D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D019012:Integrin beta1; D016023:Integrins / Q000096:biosynthesis* / Q000737:chemistry; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology*; D013585:Synovitis / Q000276:immunology* / Q000473:pathology*
D016207:Cytokines; D019012:Integrin beta1; D016023:Integrins