title: Induction of the chemokine IL-8/Kc by the articular cartilage: possible influence on osteoarthritis.
abstract: OBJECTIVE
  IL-8 and its murine equivalent keratinocyte chemoattractant (Kc), chemokines produced by chondrocytes, contribute to the pathophysiology of osteoarthritis. However, the mechanisms leading to their production are poorly known. We aimed to investigate whether mechanical (compression), inflammatory (IL-1β) and metabolic (visfatin) stresses may induce the release of Kc when applied on murine cartilage.
  
  
  METHODS
  Mouse cartilage explants were subjected to intermittent compression for 4, 6 and 24h. Primary cultures of immature murine articular chondrocytes were obtained by enzymatic digestion of articular cartilage from 6-days-old newborns mice. The effect of compression, IL-1β (10, 50, 100pg/mL) and of visfatin (5μg/mL) on the release of Kc was assessed by ELISA. IL-8 levels in conditioned media from human OA joint tissues (cartilage or synovium) were also assessed.
  
  
  RESULTS
  In comparison with non-compressed explants, loading increased Kc release of 3.2-, 1.9- and 2.0-fold at 4, 6 and 24h respectively (P<0.004, n=9). IL-1β triggered an increase of Kc release by primary cultured chondrocytes of 4.1-, 15.5- and 35.2-fold at 10, 50 and 100pg/mL of IL-1β respectively (P<0.05, n=4). Likewise, visfatin (5μg/mL) induced an increase in Kc release of 56.5±25.2 fold (P=0.002, n=6). IL-8 was released in conditioned media by synovium as well as by cartilage.
  
  
  CONCLUSIONS
  We show for the first time that IL-8/Kc is highly responsive to mechanical, inflammatory and metabolic stresses, strengthening the hypothesis that IL-8/Kc could be added to the cytokines which may have a deleterious impact in osteoarthritis.
authors.affiliation: Department of Rheumatology, Saint-Antoine Hospital, AP-HP, Pierre & Marie Curie University, 184 rue du Faubourg-Saint-Antoine, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Chauffier
authors.forename: Marie-Charlotte
authors.initials: MC
authors.lastname: Laiguillon
authors.forename: Carole
authors.initials: C
authors.lastname: Bougault
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Gosset
authors.forename: Sabrina
authors.initials: S
authors.lastname: Priam
authors.forename: Colette
authors.initials: C
authors.lastname: Salvat
authors.forename: Zvezdana
authors.initials: Z
authors.lastname: Mladenovic
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Nourissat
authors.forename: Claire
authors.initials: C
authors.lastname: Jacques
authors.forename: Xavier
authors.initials: X
authors.lastname: Houard
authors.forename: Francis
authors.initials: F
authors.lastname: Berenbaum
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D053583:Interleukin-1beta; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B; D054409:Nicotinamide Phosphoribosyltransferase; D015232:Dinoprostone