Cyr61 participates in the pathogenesis of rheumatoid arthritis by promoting proIL-1β production by fibroblast-like synoviocytes through an AKT-dependent NF-κB signaling pathway.
IL-1β plays a major role in the development of rheumatoid arthritis (RA). We previously showed that Cyr61 participates in RA pathogenesis as a proinflammatory factor. Here, we found that the levels of IL-1β and Cyr61 were higher in RA SF than in osteoarthritis (OA) SF. IL-1β mRNA and proIL-1β protein levels were remarkably increased in Cyr61-stimulated FLS; however, IL-1β was hardly detectable in the supernatant. We also found that the level of adenosine triphosphate (ATP) in SF and ST was significantly increased in RA patients and that the level of IL-1β in supernatants from Cyr61-activated FLS increased significantly when we added exogenous ATP to the culture. Mechanistically, Cyr61 induced proIL-1β production in FLS via the AKT-dependent NF-κB signaling pathway, and ATP caused Cyr61-induced proIL-1β to generate IL-1β in a caspase-1-dependent manner. Our results reveal a novel role of Cyr61 in RA that involves the promotion of proIL-1β production in FLS.
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Affiliated Union Hospital of Fujian Medical University, Fuzhou, PR China.
Xianjin
X
Zhu
Affiliated Renmin Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, PR China.
Yanfang
Y
Song
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Rongfen
R
Huo
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Jie
J
Zhang
Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, PR China.
Songtao
S
Sun
Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, PR China.
Yong
Y
He
Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, PR China.
Huali
H
Gao
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Miaojia
M
Zhang
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Xiaoxuan
X
Sun
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Tianhang
T
Zhai
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Huidan
H
Li
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Yue
Y
Sun
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Zhou
Z
Zhou
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Baihua
B
Shen
Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, PR China. Electronic address: 13701888178@163.com.
Lianbo
L
Xiao
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. Electronic address: ninglixiaoxue57@163.com.
Ningli
N
Li
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology
C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D020170:Caspase 1
Cyr61; Fibroblast-like synoviocyte; IL-1β; Rheumatoid arthritis