Hepatocyte growth factor [HGF], HGF activator [HGFA] and c-met expression in rheumatoid synovial tissues in relation to disease activity

We examined the localization and mRNA expression of HGF, HGFA and c-Met in synovial tissues [ST] in rheumatoid arthritis [RA] in relation to disease activity to characterize its biologic function in that disease. Immunohistochemical staining and RT-PCRfor HGF, HGFA and c-Met were performed on ST specimens from 34 RA-patients and 20 osteoarthritis [OA] controls. Synovial fluid [SF] samples were taken from all RA and OA for measuring HGF with ELISA technique. Immunohistochemical staining of RAST revealed that HGFA and c-Met were strongly expressed infibroblasts, macrophages, endothelial cells and less so on synovial lining cells. But HGF was expressed faintly in macrophages andfibroblasts. While, in OAST, HGFA and c-Met were detected in the same cells as RAST but in a different distribution. HGF was localized in vascular endothelial cells. RT-PCR showed HGF, HGFA and c-Met mRNA in all RAST and all OAST. HGF levels in SF samples were higher in RA patients [range 5.6-39.2 ng/ml and mean 26.3 +/- 1.2 ng/ml] than OA controls [range 4.2-37.5 ng/ml and mean 11.2+2.4 ng/ml]. The differences were statistically significant [p<0.001]. A non-significant correlation was found between HGF-SF levels and disease activity score [DAS] [p>0.5]. HGFA, HGF and c-Met mRNA are expressed in ST in RA and OA. Lack of correlation between HGF-SF levels and DAS indicated that HGF played a regulatory role in the immunopathogenesis of RA

role of interleukin-16 in the immunopathogenesis of rheumatoid arthritis

We analyzed, interleukin-16 [IL-16], in relation to disease activity to characterize its biologic function in RA. Secreted IL-16 was measured with enzyme immunoassay in the sera from 30 RA patients and 30 apparently healthy controls as well as in synovial fluid [SF] from 16 RA patients and 15 patients with non-RA synovitis as controls. IL-16 expression in peripheral blood mononuclear cells [PBMC] was characterized with flow cytometric analysis after intracellular cytokine staining for IL-16. In synovial tissue specimens, both were done: immunohistochemistry for localization of IL-16, and histopathology, in which the tissue was scored semiquantitatively for synovial hyperplasia and cellular infiltration. IL-16 was detected at significantly higher levels in sera and SF of RA patients in comparison to apparently healthy controls and non-RA synovitis [p < 0.001 and p<0.0001 respectively]. Also, IL-16 was detected significantly higher in SF in comparison to sera in RA patients [p<0.001]. Flow cytometry of PBMC showed that a great proportion of both CD4+ and CD8+ cells expressed IL-16 protein. Also, immunohisto-chemistry revealed more CD4+ and less frequency of CD8+ cells in synovial infiltration. A significant correlation between IL-16 expression and local inflammatory activity could not be established [p>0.21] with microscopic analysis of the synovial cells infiltrate. In addition, no significant association was observed between serum, SF, and synovial tissue expression of IL -16 and clinical disease activity in RA [p>0. 61, p>0.5 and p> 0. 42 respectively]. IL-16 seems to play a regulatory rather than a proinflammatory role in the immunopathogenesis of RA