Altered integrin expression in rheumatoid synovial lining type B cells: in vitro cytokine regulation of alpha 1 beta 1, alpha 6 beta 1, and alpha v beta 5 integrins.
OBJECTIVE
We recently showed that in rheumatoid arthritis (RA) the extracellular matrix around the lining cells is similar to the matrix seen in osteoarthritis, whereas the cellular adhesion apparatus is very different. In hyperplastic synovial membrane there is very little of alpha 6, alpha v, and beta 5 integrin subunits, whereas in noninflammatory synovial membrane these integrins are well expressed. We studied how expression of these cell adhesion molecules is regulated in RA in vitro.


METHODS
The integrin expression in 6 different synovial fibroblast strains representing the type B cells and in THP-1 cell line was examined by immunoprecipitation, flow cytometry, and Northern hybridization.


RESULTS
Proinflammatory cytokines, especially interleukin 1 beta, increased the expression of alpha 1 integrin in synovial fibroblasts. When the monocyte-like THP-1 cells were induced to differentiate to adherent macrophages they started to express alpha 6 and beta 5 integrin subunits. In adherent THP-1 cells the expression of integrin alpha 6 subunit was strongly enhanced by transforming growth factor-beta and downregulated by the combination of tumor necrosis factor-alpha and interferon-gamma.


CONCLUSIONS
Cytokines regulate the cell adhesion molecules of synovial fibroblasts and mononuclear phagocytes in vitro causing alterations in integrin expression similar to the ones seen in rheumatoid synovium in vivo.
Department of Medical Biochemistry, MediCity Research Laboratory, University of Turku, Finland.
L
L
Pirilä
J
J
Heino
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015152:Blotting, Northern; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D039222:Integrin alpha1beta1; D039121:Integrin alpha6beta1; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects; D011233:Precipitin Tests; D019030:Receptors, Vitronectin / Q000378:metabolism; D013583:Synovial Membrane / Q000737:chemistry; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D039222:Integrin alpha1beta1; D039121:Integrin alpha6beta1; D019012:Integrin beta1; D016023:Integrins; D007375:Interleukin-1; D019030:Receptors, Vitronectin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C064660:integrin alphaVbeta5; D007371:Interferon-gamma; D010959:Tissue Plasminogen Activator