Induction of interleukin-23 p19 by serum amyloid A (SAA) in rheumatoid synoviocytes.
In this study, we investigated the roles of serum amyloid A (SAA) in T helper 17 (Th17)-related cytokine induction in rheumatoid arthritis (RA) synoviocytes. Synoviocytes isolated from rheumatoid arthritis (RA) patients were stimulated with recombinant SAA and IL-23 expression was investigated using reverse transcriptase-polymerase chain reaction and Western blot. The involvement of mitogen-activated protein kineases (MAPKs) and nuclear factor (NF)-κB in SAA-induced interleukin (IL)-23 p19 expression was investigated using pharmacological inhibitors. In RA synoviocytes, SAA induced the expression of IL-23 p19 and p40 mRNA expression. The SAA-stimulated expression of p19 was rapid (< 3 h), and insensitive to polymyxin B treatment. This SAA-stimulated expression of IL-23 p19 was inhibited completely by inhibitors of NF-κB, p38MAPK and dexamethasone. Interestingly, the SAA-induced IL-23, p19 and p40 production was accompanied by enhanced expression of IL-1β, but not transforming growth factor-β. These results indicate that SAA is a significant inducer of IL-23 and IL-1β in RA synoviocytes and potentially activates the IL-23/IL-17 pathway in the RA synovium. Our data present a novel interaction between inflammation and autoimmunity by an acute-phase protein.
Migita
K
K
Department of Rheumatology, NHO Nagasaki Medical Center, Kubara, Omura, Japan. migita@nmc.hosp.go.jp
Koga
T
T
Torigoshi
T
T
Motokawa
S
S
Maeda
Y
Y
Jiuchi
Y
Y
Izumi
Y
Y
Miyashita
T
T
Nakamura
M
M
Komori
A
A
Ishibashi
H
H
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D053760:Interleukin-23 Subunit p19 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053583:Interleukin-1beta; D053760:Interleukin-23 Subunit p19; D016328:NF-kappa B; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D048051:p38 Mitogen-Activated Protein Kinases