title: Vascular cell adhesion molecule 1 (CD106) on primary human articular chondrocytes: functional regulation of expression by cytokines and comparison with intercellular adhesion molecule 1 (CD54) and very late activation antigen 2.
abstract: OBJECTIVE
  To investigate the expression of adhesion molecules belonging to the immunoglobulin superfamily on human primary articular chondrocytes and to determine their response pattern to cytokines with respect to the adhesion of lymphocytes.
  
  
  METHODS
  The expression of adhesion molecules was studied by flow cytometry (cultured cells), immunohistochemistry (cartilage), reverse transcription-polymerase chain reaction, and Northern blotting. Adhesion of T cells to chondrocytes was measured using the Jurkat T cell line.
  
  
  RESULTS
  Vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) were found to be constitutively expressed on large percentages of unstimulated chondrocytes in culture and in cartilage ex vivo. ICAM-2, ICAM-3, and very late activation antigen 4 (VLA-4; alpha4beta1 integrin), the ligand for VCAM-1, were not detected. Interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) further induced VCAM-1 and ICAM-1 messenger RNA and protein expression. Transforming growth factor beta (TGFbeta) had no effect on ICAM-1 and decreased the expression of VCAM-1. Another adhesion molecule, VLA-2 alpha2beta1 integrin) that was also expressed on unstimulated chondrocytes, was differentially regulated by cytokines. While neither IL-1beta nor TNFalpha had any effect on expression of VLA-2, TGFbeta markedly increased the alpha2 subunit of VLA-2. Adhesion of Jurkat T cells to chondrocytes was further induced by IL-1beta and TNFalpha. Pretreatment of chondrocytes with monoclonal antibodies to VCAM-1 and ICAM-1 inhibited adhesion of T cells to chondrocytes.
  
  
  CONCLUSIONS
  VCAM-1, ICAM-1, and VLA-2 are constitutively expressed by human articular chondrocytes. Expression is regulated by cytokines. As shown for other chondrocyte genes, IL-1beta/TNFalpha and TGFbeta antagonistically modulate the expression of adhesion molecules. VCAM-1 and ICAM-1 contribute to adhesion of T lymphocytes to chondrocytes, and may thus participate in host defense mechanisms during inflammatory joint conditions such as rheumatoid arthritis and after cartilage transplantation.
authors.affiliation: Albert-Ludwig University, Freiburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kienzle
authors.forename: J
authors.initials: J
authors.lastname: von Kempis
mesh_terms: D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D038981:Receptors, Collagen; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D007375:Interleukin-1; D012333:RNA, Messenger; D038981:Receptors, Collagen; D016201:Receptors, Lymphocyte Homing; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1