Local expression of acute phase serum amyloid A mRNA in rheumatoid arthritis synovial tissue and cells.

Abstract

Serum amyloid A (SAA) protein, a bioactive protein produced during inflammation, is present in synovial fluid (SF) of patients with rheumatoid arthritis (RA). Based on our recent finding that SF SAA concentration exceeded the serum counterpart in some patients with RA, we examined the local steady state concentration of SAA mRNA isoforms in synovia and in synovial cells cultured from patients with RA and osteoarthritis (OA). Total cellular RNA from synovial membranes of patients with RA or OA and from cultured synovial cells of patients with RA was analyzed by reverse transcription polymerase chain reaction and Northern blot. Acute phase SAA (A-SAA) mRNA isoforms were detected only in RA synovia, but not in OA synovia; however, the constitutive SAA (C-SAA) mRNA isoform was detected in similar abundance in both OA and RA synovia. There was evidence of C-SAA, but not A-SAA mRNA in cultured synovial cells at quiescence. After stimulation with both 1 mM dexamethasone and 10 ng/ml interleukin 1beta (IL-1beta), the quantity of steady state A-SAA muRNA in cultured synovial cells was markedly increased. Both A-SAA and C-SAA mRNA are detectable in RA synovia, while only C-SAA mRNA is detectable in OA and in quiescent cultured synovial cells. The steady state A-SAA mRNA isoform in cultured synovial cells was markedly increased in the presence of dexamethasone plus IL-1beta. The local synthesis of A-SAA may contribute, at least in part, to the concentration of A-SAA protein in SF and may contribute to the altered molecular and cellular physiology in RA joints.