title: Peroxisome proliferator-activated receptor-gamma expression in monocytes/macrophages from rheumatoid arthritis patients: relation to disease activity and therapy efficacy--a pilot study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Sciences of Health, Via Solaroli 17, 28100 Novara, Italy.
authors: Alessandra
authors: A
authors: Palma
authors: Pier Paolo
authors: PP
authors: Sainaghi
authors: Angela
authors: A
authors: Amoruso
authors: Luigia Grazia
authors: LG
authors: Fresu
authors: Giancarlo
authors: G
authors: Avanzi
authors: Mario
authors: M
authors: Pirisi
authors: Sandra
authors: S
authors: Brunelleschi
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D010865:Pilot Projects; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D020780:Matrix Metalloproteinase 9