EXPRESSION OF ARTHRITIS-CAUSING HLA-B27 ON HELA-CELLS PROMOTES INDUCTION OF C-FOS IN RESPONSE TO IN-VITRO INVASION BY SALMONELLA-TYPHIMURIUM

HLA-B27 confers a very strong genetic predisposition to development of a reactive arthritis after infection by bacteria such as Salmonella t yphimurium, This study examines the role of HLA-B27 in the initiation of the earliest host activities after exposure to Salmonella, namely a ctivation of the immediate early genes in the epithelial cells, Our ma jor finding is that in Hela cells, the expression of c-fos was induced by Salmonella invasion only when the cells expressed the transfected HLA-B27 gene, but not the HLA-A1 gene or a truncated HLA-B27 gene lack ing the exons encoding the cytoplasmic domain, C-fos is potentially ca pable of complexing with members of the c-jun family to become the AP- 1 transcription complex. Parallel to c-fos expression, we found that o nly with the HLA-B27 transfectant was there expression of AP-1, AP-1 p otentially controls the expression of a large number of genes, On scre ening a panel of proinflammatory molecules, we found that Salmonella i nvasion induced expression of monocyte chemoattractant protein-1 in th e HLA-B27 cells, Since each of these separate positive findings belong to the same cascade of events after cell activation, together they re inforce the hypothesis that HLA-B27 plays a modulatory role in the ear ly signal transduction events induced by Salmonella invasion, This hyp othesis adds another item to the list of allele-specific activities ca rried out by HLA class I molecules. If similar activation also occurs in the joints, it may play a major role in arthritis.