Bacterial peptidoglycan stimulates integrin expression and MMP production of synovial fibroblasts

Bacterial products such as peptidoglycan (PGN) have been found in joints of patients with rheumatoid arthritis. Recently, it has been shown that intra-articular injection of bacterial PGN can induce a transient arthritis in mice, indicating a possible role of bacterial products in the pathogenesis of arthritis. Whereas the activation of macrophages by PGN is established, it is not known whether synovial fibroblasts are also able to respond. We studied the activation marker expression of human synovial fibroblasts in culture after incubation with or without PGN in vitro. Cultured human synovial fibroblasts derived from RA patients were incubated in presence or absence of PGN. After culture periods of 24 to 48 hours the surface expression of integrins was measured by FACS using directly labeled antibodies. Expression of various matrix metallopro-teinases (MMP) was determined by real time PCR (TaqMan).

PGN resulted in an upregulation of the surface expression of CD54 (ICAM-1) as compared to untreated cultures. In the tested cultured RA synovial fibroblasts the upregulation in responders ranged between 20% and 100%. PGN also upregulated the expression of MMP-3 and MMP-1 mRNA. These results suggest that the presence of bacterial PGN can activate synovial fibro-blasts, to express ICAM-1 and MMPs. This activation might represent an important early step in the development of inflammatory arthritis.