Beta 1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients.
Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA), whereas the mechanisms for constitutive production of inflammatory cytokines in affected joints are largely unknown. Recently, integrin-mediated interaction with extracellular matrix (ECM) proteins has been demonstrated to play a role in regulating cytokine production in T cells and monocytes. In this study, we investigated the contribution of the beta 1 integrin-mediated interaction with ECM proteins to the persistent cytokine gene expression in RA synovial fluid mononuclear cells (SFMNC). We examined mRNA expression of 14 cytokines in the SFMNC of three RA patients, which were either fresh or cultured overnight in serum-free medium on ECM-coated plates, by polymerase chain reaction with a panel of oligonucleotide primers specific for each cytokine. The persistent expression of various cytokine mRNA found in fresh SFMNC was maintained after overnight culture in serum-free medium on ECM proteins, especially on laminin (LM), but not on serum albumin. This effect of LM was inhibited by an anti-integrin beta 1 chain (CD29) mAb, as well as by an anti-CD3 mAb, indicating an important role of the beta 1 integrin-mediated interaction with ECM proteins in regulating persistent cytokine gene expression in RA SFMNC, and a key role of T cells in regulating inflammatory monokine production.
Miyake
S
S
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Yagita
H
H
Maruyama
T
T
Hashimoto
H
H
Miyasaka
N
N
Okumura
K
K
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004347:Drug Interactions; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013582:Synovial Fluid / Q000166:cytology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D016895:Culture Media, Serum-Free; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D012333:RNA, Messenger