title: Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).
  
  
  METHODS
  Celastrol was administered to AIA rats both in the early (4 days after disease induction) and late (11 days after disease induction) phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively.
  
  
  RESULTS
  Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects.
  
  
  CONCLUSIONS
  Our results validate celastrol as a promising compound for the treatment of arthritis.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Cascão
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vidal
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Inês P
authors.initials: IP
authors.lastname: Lopes
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Eunice
authors.initials: E
authors.lastname: Paisana
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Rino
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Moita
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.|Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon Academic Medical Centre, Lisbon, Portugal.
authors.forename: João E
authors.initials: JE
authors.lastname: Fonseca
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000276:immunology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D005260:Female; D015870:Gene Expression; D006801:Humans; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D053978:Pentacyclic Triterpenes; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D000097382:CD68 Molecule
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053583:Interleukin-1beta; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C050414:celastrol