Serum amyloid A protein stimulates CCL20 production in rheumatoid synoviocytes.
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.
Migita
Kiyoshi
K
Department of Rheumatology, Clinical Research Center, NHO Nagasaki Medical Center, Omura, Japan. migita@nmc.hosp.go.jp
Koga
Tomohiro
T
Torigoshi
Takafumi
T
Maeda
Yumi
Y
Miyashita
Taichiro
T
Izumi
Yasumori
Y
Aiba
Yoshihiro
Y
Komori
Atsumasa
A
Nakamura
Minoru
M
Motokawa
Satoru
S
Ishibashi
Hiromi
H
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
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