Continuous enhanced expression of Hsc70 but not Hsp70 in rheumatoid arthritis synovial tissue

To investigate the expression of constitutive and inducible members of the Hsp70 protein family in synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis (OA).

Frozen sections of synovial tissue and isolated synovial adherent cells obtained from 17 RA patients, 5 OA patients, and 1 patient with carpal tunnel syndrome (CTS) were analyzed with specific monoclonal antibodies, by immunohistochemistry, immunocytochemistry, and immunoblotting.

Expression of the constitutive chaperone Hsc70 was increased in synovial tissue from 9 of 9 patients with RA, but was faint or undetectable in 3 of 3 samples from patients with OA. In RA samples, cells mainly of the synovial lining stained intensely for Hsc70 as well as for HLA-DR, CD14, and CD68. Also, in vitro-cultured synovial adherent cells from 8 of 9 RA patients overexpressed Hsc70 (specimens from 1 RA patient were used in both the immunochemistry and the in vitro culture studies). On immunoblots of protein extracts, the synovial and HeLa cell molecules appeared identical in size. The inducible chaperone Hsp70 was not detected in samples from any of the same 17 RA patients, except for rare, isolated cells in 3. Samples from 4 of 5 OA patients also were negative for the inducible chaperone Hsp70, and the fifth was very weakly positive. In addition, tissue from 1 patient with CTS was analyzed 10 months before diagnosis of RA. Synovial tissue from this patient showed extreme overexpression of both Hsc70 and Hsp70.

In RA, synovial lining cells continuously overexpress Hsc70 but not Hsp70. Hsc70 may be up-regulated due to the high activity of these cells in several respects, including antigen processing and presentation.