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배양된 연골세포에서 각종 Cytokine과 성장인자가 β1-integrin 및 ICAM-1의 발현에 미치는 영향
송관규 ( Gwan Gyu Song ),노영무 ( Young Moo Ro ),유대현 ( Dae Hyu Yoo ),김성윤 ( Seong Yoon Kim ) 대한류마티스학회 1995 대한류마티스학회지 Vol.2 No.1
Objective: The cell-cell and cell-extracellular matrix interactions are critical to the embryogenesis, morphogenesis, maintenance of tissue integrity, and function of cells. This interactions are mediated by membrane glycoproteins called adhesion molecules. βl-integrins are heterodimeric transmembrane glycopro-teins which play critical roles in the ability of cells to elaborate and maintain extracellular matrix. ICAM-l is a sialylated glycoprotein and mediates various cell-cell interactions in immunity and inflammation. Articular cartilage consists of chondrocytes embedded in an extensive extracellular matirx. In normal tissue, the chondrocytes actively effect the stable equili-brium between the synthesis and degradation of matrix components, so that a constant concentration of these components is maintained. In osteoarthritis, the stable equilibrium is disrupted and the rate of loss of proteoglycan exceeds the rate of depositon of newly synthesized moleclues. This equilibrium is influenced by cytokines and growth factors such as IL-I, TNF-α, IGF-1 and TGF-β. Integrins and their ligands may mediate some of the interactions of chondrocytes and cellular matrix, and the cytokines and local growth factors may affect the expression of integrins on chondrocytes. ICAM-1 may mediate interactions with other cells in osteoarthritic joint, and also may be modulated by cytokines and growth factors. The effect of IL-I, TNF-α, IGF-1 and TGF-β in the expression of, β1-integrin (CD29) and ICAM-1(CD54) on chondrocytes was investigated. Methods: Cultured chondrocytes(3rd passages) from 2 osteoarthritc patient were used. Cells were incubated for 24hours with and without IL-1β 25U/ml, IL-l 50U/ml, TNF-α 1ng/ml, TNF-α 10ng/ml, IFN-γ 100U/ml, IGF-1 10ng/ml, IGF-1 50ng/ml, IGF-1 100ng/ml, TGF-β 10ng/ml, and TGF-β 30ng/ml. Chondrocytes were stained with monoclonal antibodies against, β1-integrin (CD29) and ICAM-1 (CD54), and positve cells were counted under the light microscpe. Results: 1) Cultured chondrocytes readily expressed, β1-integrin (82.9%). 2) β1-integrin was down-regulated by IL-1β(75.4%), TNF-α(61.2%), and TGF-β (77.0%), and was slightly up-regulated by IFN-γ(85.0%) and IGF-1 (88.9%). 3) ICAM-1 was presented in only 18.0% of cells. 4) Expression of ICAM-1 was readily up-regulated by IL-1β(84.0%) and TNF-α(80.3%), and mildly up-regulated by IFN-γ(33.0%), IGF-1(35.0%), and TGF-β(29.3%). Conclusions: The presence of, 81-integrin and ICAM-1 on chondrocytes and the modulation of their expression by cytokines and local growth factors suggest that they have important roles in the interaction of chondrocytes with cartilage matrix and with other cells of osteoarthritic joints. Their roles should be elucidated by further researches.
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