title: Differential expression of interleukin-17 and interleukin-22 in inflamed and non-inflamed synovium from osteoarthritis patients.
abstract: OBJECTIVE
  Synovitis associated with osteoarthritis (OA) is directly responsible for several clinical symptoms and reflects OA's structural progression. This study sought to analyze the expression of proinflammatory mediations, including Interleukin (IL)-17 and IL-22, which play key roles in regulating inflammatory processes, in inflamed and non-inflamed areas of osteoarthritic synovium.
  
  
  METHODS
  Synovium from knees of 32 OA patients were collected at surgery. Macroscopic evaluation of inflammation enabled inflamed and non-inflamed areas to be separated. Samples were incubated to obtain tissue-conditioned media. Quantitative mRNA expression of proinflammatory mediators was analyzed by RT-PCR and protein levels by ELISA and gelatin zymography. Immunohistochemistry and histology were performed.
  
  
  RESULTS
  Inflamed synovium were characterized by increased leukocyte infiltration and a higher vessel-to-tissue area ratio than non-inflamed tissues. Macrophages, T and B lymphocytes, and some neutrophils were found only in the inflamed tissue, and only in the subintimal layer. Levels of proinflammatory cytokines and MMP-9 were significantly higher in tissue-conditioned media from inflamed than non-inflamed tissues. Inflamed areas were associated with higher expression of IL-17 and IL-22, both correlated with the combined release of IL-6, IL-23, and TGFβ1.
  
  
  CONCLUSIONS
  Our results showed that inflammatory cytokines, including IL-17 and IL-22, are expressed at higher levels by inflamed OA synovium and suggest IL-22 involvement in OA pathophysiology. This study will help identify new therapeutic strategies for OA, especially the targeting of IL-22 to decrease inflammation.
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Deligne
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Casulli
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Pigenet
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Bougault
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Campillo-Gimenez
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France; Department of Orthopaedic Surgery and Traumatology, Assistance Publique - Hôpitaux de Paris, Saint-Antoine Hospital, 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Nourissat
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France; Department of Rheumatology, Assistance Publique - Hôpitaux de Paris, Saint-Antoine Hospital, 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France. Electronic address: francis.berenbaum@sat.aphp.fr.
authors.forename: F
authors.initials: F
authors.lastname: Berenbaum
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Elbim
authors.affiliation: Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Houard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism*; D013585:Synovitis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D012313:RNA; D000097043:Interleukin-22
keywords: IL-17; IL-22; Osteoarthritis; Synovial inflammation