title: Serum amyloid A protein stimulates CCL20 production in rheumatoid synoviocytes.
abstract: OBJECTIVE
  Although serum amyloid A (SAA) has been used as a marker of inflammation, its role in leucocyte recruitment and angiogenesis has not been well established in RA. CCL20 is a chemokine involved in the migration of CCR6-expressing Th17 cells. To study the contribution of SAA to the recruitment of Th17 cells, we investigated the effects of SAA on CCL20 production by RA synoviotytes.
  
  
  METHODS
  Synoviocytes isolated from RA patients were stimulated with recombinant SAA and cellular supernatants were analysed by CCL20-specific ELISA. CCL-20 mRNA expression was analysed by RT-PCR.
  
  
  RESULTS
  SAA is a most potent inducer of CCL20 secretion in RA synoviocytes compared with other inflammatory cytokines (IL-1beta, TNF-alpha and IL-17A). SAA stimulation induced CCL20 mRNA expression in RA synoviocytes, which was not affected by polymyxin B pre-treatment. SAA-induced CCL20 production was down-regulated by NF-kappaB inhibition and partially by c-jun N-terminal kinase (JNK) inhibition. SAA-induced CCL20 production was also suppressed by dexamethasone or FK506.
  
  
  CONCLUSIONS
  These findings suggest that SAA may be implicated in the recruitment of lymphocytes, including CCR6-expressing Th17 cells, in RA synovium by up-regulating CCL20 production in synoviocytes.
authors.affiliation: Department of Rheumatology, Clinical Research Center, NHO Nagasaki Medical Center, Omura, Japan. migita@nmc.hosp.go.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Koga
authors.forename: Takafumi
authors.initials: T
authors.lastname: Torigoshi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Maeda
authors.forename: Taichiro
authors.initials: T
authors.lastname: Miyashita
authors.forename: Yasumori
authors.initials: Y
authors.lastname: Izumi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Aiba
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Komori
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.forename: Satoru
authors.initials: S
authors.lastname: Motokawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007118:Immunoassay / Q000379:methods; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D018501:Antirheumatic Agents; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D016559:Tacrolimus