The effect of cytokines on the expression of MHC antigens and ICAM-1 by normal and transformed synoviocytes.
We report the expression on synovial cells of cell surface molecules known to be involved in T cell activation by antigen presenting cells. Normal human synovial fibroblasts and a human synovial cell line transformed with the SV40 large T antigen were used for in vitro stimulation studies with recombinant cytokines. We demonstrate an increase in MHC-A, B, C expression in normal synovial cells in response to recombinant interferon gamma (r gamma IFN), tumour necrosis factor alpha and beta (rTNF alpha and beta) and interleukin-1 (rIL-1 alpha). Intercellular adhesion molecular-1 (ICAM-1) expression was increased in parallel with MHC Class I. The combination of r gamma IFN and rTNF alpha was additive in its effect on ICAM-1 expression. Northern blot analysis suggests that ICAM-1 expression in synovial cells is controlled at the level of transcription. In contrast, MHC Class II (HLA-DR) was only significantly induced by r gamma IFN. Other stimuli including interleukin-4 (IL-4), interleukin 6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF) and prostaglandin E2 (PGE2) did not affect the expression of ICAM-1 or MHC Class I and II. Leucocyte function antigen 3 (LFA-3) expression was not affected by any of the stimuli tested. Immunoperoxidase staining of rheumatoid synovial tissue confirmed enhanced in vivo expression of ICAM-1 in rheumatoid arthritis. These changes are discussed in the context of T cell activation in inflammatory arthritis.
Lions Laboratory, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Australia.
I P
IP
Wicks
T
T
Leizer
S O
SO
Wawryk
J R
JR
Novotny
J
J
Hamilton
G
G
Vitti
A W
AW
Boyd
D001172:Arthritis, Rheumatoid / Q000276:immunology; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002461:Cell Line, Transformed; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D013583:Synovial Membrane / Q000276:immunology*
D015815:Cell Adhesion Molecules; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1