title: The chemokine CCL20 induces proinflammatory and matrix degradative responses in cartilage.
abstract: BACKGROUND
  Local inflammation plays a role in the pathophysiology of osteoarthritis (OA) and chemokines exert catabolic effects on articular cartilage either through paracrine and/or autocrine mechanisms. We sought to compare the expression levels of the chemokine (C-C motif) ligand 20 (CCL20) and its chemokine receptor 6 (CCR6) in donor and osteoarthritic (OA) cartilage and to investigate the role of CCL20 in the pathogenesis of OA and chondrocyte phenotype.
  
  
  METHODS
  Cartilage/chondrocytes from donor and OA knee joints was analyzed for CCL20 and CCR6 expression by RT-PCR and immunohistochemistry. Effects of CCL20 on cytokines and mediators of cartilage degradation were examined by RT-PCR for mRNA expression levels, enzyme-linked immunosorbent assays, and proteoglycan (GAG) assays.
  
  
  RESULTS
  CCL20 and CCR6 proteins were abundantly expressed in OA cartilage sections compared to donor sections as judged by immunohistochemistry. RT-PCR of cartilage extracts confirmed the predominance of CCL20/CCR6 mRNA expression in OA cartilage. CCL20 mRNA expression was low in donor chondrocytes but increased after stimulation with proinflammatory cytokines. mRNA expression levels of IL-6, cyclooxygenase-2, and iNOS were elevated in donor chondrocyte cultures treated with rhCCL20. The release of MMP1/13, PGE2, proteoglycan GAG fragments, and IL-6 from cartilage explant cultures was markedly augmented in the presence of CCL-20. CCL-20 stimulated MMP-13, ADAMTS-5, and col type X mRNA but inhibited col type II mRNA expression in freshly explanted and cultured cartilage specimens.
  
  
  CONCLUSIONS
  CCL20/CCR6 may play an important role in the pathogenesis of OA by inducing changes in phenotype and catabolic gene expression in chondrocytes.
authors.affiliation: Faculty of Medicine, St Joseph University, Regenerative Medicine and Inflammation lab, Beirut, 11-5076, Lebanon, nada.aladdin@gmail.com.
authors.forename: Nada
authors.initials: N
authors.lastname: Alaaeddine
authors.forename: John
authors.initials: J
authors.lastname: Antoniou
authors.forename: Mayssam
authors.initials: M
authors.lastname: Moussa
authors.forename: George
authors.initials: G
authors.lastname: Hilal
authors.forename: Gaby
authors.initials: G
authors.lastname: Kreichaty
authors.forename: Ismat
authors.initials: I
authors.lastname: Ghanem
authors.forename: Wissam
authors.initials: W
authors.lastname: Abouchedid
authors.forename: Elie
authors.initials: E
authors.lastname: Saghbini
authors.forename: John A
authors.initials: JA
authors.lastname: Di Battista
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000071116:ADAMTS5 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism*; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D019902:Chondrocytes / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009573:Nitrites / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; C508600:IL6 protein, human; D015850:Interleukin-6; D009573:Nitrites; D011509:Proteoglycans; D012333:RNA, Messenger; D054399:Receptors, CCR6; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13