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

Objectives. Peroxisome proliferator-activated receptor-gamma (PPARg) is expressed by different cell types in the joints and plays a relevant anti-inflammatory role in various diseases. This pilot study aimed to evaluate PPARg expression in monocytes/macrophages isolated from RA patients as compared with healthy subjects, the relationships between PPARg expression, MMP-9 activity and disease, and the influence of therapy with anti-rheumatic drugs on these parameters. 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. PPARg 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- 12,14 prostaglandin J2 (15d-PGJ, a PPARg agonist), MTX and methylprednisolone (MP) to affect PPARg expression and lipopolysaccharide (LPS)-induced MMP-9 activity. Results. Monocytes/MDMs from RA patients have significantly enhanced PPARg 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. At therapeutic concentrations, MTX and MP increase in vitro PPARg protein expression and inhibit LPS-induced MMP-9 activity. Conclusion. PPARg 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.