Peroxisome proliferator-activated receptor-gamma expression in monocytes/macrophages from rheumatoid arthritis patients: relation to disease activity and therapy efficacy-a pilot study

Methods. Thirty RA patients of both sexes (treated with CSs and MTX, mainly) and 15 healthy volunteers were enrolled in this study. Disease severity was evaluated by the 28-joint disease activity score (DAS-28). Monocytes and monocyte-derived macrophages (MDMs) were isolated by standard procedures. PPAR gamma protein and mRNA expression were assessed by immunoblotting and real-time PCR, respectively; MMP-9 activity was determined by gelatin zymography. Moreover, we checked the ability of 15-deoxy-delta(12,14)-prostaglandin J(2) (15d-PGJ, a PPAR gamma agonist), MTX and methylprednisolone (MP) to affect PPAR gamma expression and lipopolysaccharide (LPS)-induced MMP-9 activity. Results. Monocytes/MDMs from RA patients have significantly enhanced PPAR gamma expression (both protein and mRNA) and MMP-9 activity as compared with healthy donors. Interestingly, cells from patients with less active disease (DAS-28 < 3.2) present higher PPAR gamma protein expression and lower MMP-9 activity than RA patients with DAS-28 > 3.2. At therapeutic concentrations, MTX and MP increase in vitro PPAR gamma protein expression and inhibit LPS-induced MMP-9 activity. Conclusion. PPAR gamma expression in human monocytes/MDMs could represent an indicator of disease activity and therapy efficacy in RA because patients with a DAS-28 score < 3.2 show the highest expression.