Serum amyloid A-induced IL-6 production by rheumatoid synoviocytes.
In this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogen-activated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-kappaB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-kappaB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis.
Koga
Tomohiro
T
Clinical Research Center and Department of Rheumatology, NHO Nagasaki Medical Center, Omura, Japan.
Torigoshi
Takafumi
T
Motokawa
Satoru
S
Miyashita
Taichiro
T
Maeda
Yumi
Y
Nakamura
Minoru
M
Komori
Atsumasa
A
Aiba
Yoshihiro
Y
Uemura
Takashi
T
Yatsuhashi
Hiroshi
H
Ishibashi
Hiromi
H
Eguchi
Katsumi
K
Migita
Kiyoshi
K
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D013582:Synovial Fluid / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C105101:FPR2 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D000685:Serum Amyloid A Protein; D051996:Transcription Factor RelA; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases