The Effect Of Cytokines And Local Growth Factors In The Expreession Of Fil-Integrin And Icam-1 On Cultured Chondrocyte

Song, Gwan Gyu; Ro, Young Moo; Yoo, Dae Hyun; Kim, Seong Yoon

Abstract

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. fil-integrins are heteredimeric transmembrane glycoproteins which play critical roles in the ability of cells to elaborate and maintain extracellular matrix. ICAM-1 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 cytok{nes and growth factors such as IL-1, TNF-alpha, IGF-1 and TGF-beta. 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-1, TNF-alpha, IGF-1 and TGF-beta in the expression of fil-integrin(CD29) and ICAM-l(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-lfi 25U/ml, IL-l 50U/ml, TNF-alpha lng/ml, TNF-alpha 10ng/ml, IFN-gamma 100U/ml, IGF-1 10ng/ml, IGF-1 50ng/ml, IGF-1 100ng/ml, TGF-beta 10ng/ml, and TGF-beta 30ng/ml. Chondrocytes were stained with monoclonal antibodies against beta1-integrin(CD29) and ICAM-1 (CD54), and positve cells were counted under the light microscpe.
RESULTS
1) Cultured chondrocytes readily expressed fi1-integrin(82. 9%). 2) filintegrin was down-regulated by IL-1beta(75.4%), TNF-alpha(61.2%), and TGF-beta (77.0%), and was slightly up-regulated by IFN-gamma(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-1beta(84.0%) and TNF-alpha(80.3%), and mildly up-regulated by IFN-gamma(33.0%), IGF-1 (35.0%), and TGF-beta(29.3%).
CONCLUSIONS
The presence of fil-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.