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

摘要

Objectives: Peroxisome proliferator-activated receptor-gamma (PPARγ) 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 PPARγ expression in monocytes/macrophages isolated from RA patients as compared with healthy subjects, the relationships between PPARγ 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. PPARγ 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-Δ 12,14-prostaglandin J 2 (15d-PGJ, a PPARγ agonist), MTX and methylprednisolone (MP) to affect PPARγ expression and lipopolysaccharide (LPS)-induced MMP-9 activity.Results: Monocytes/MDMs from RA patients have significantly enhanced PPARγ 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 PPARγ protein expression and lower MMP-9 activity than RA patients with DAS-28 3.2. At therapeutic concentrations, MTX and MP increase in vitro PPARγ protein expression and inhibit LPS-induced MMP-9 activity.Conclusion: PPARγ 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.