title: CD147 promotes IKK/IκB/NF-κB pathway to resist TNF-induced apoptosis in rheumatoid arthritis synovial fibroblasts.
abstract: TNF is highly expressed in synovial tissue of rheumatoid arthritis (RA) patients, where it induces proinflammatory cytokine secretion. However, in other cases, TNF will cause cell death. Considering the abnormal proliferation and activation of rheumatoid arthritis synovioblasts, the proper rate of synovioblast apoptosis could possibly relieve arthritis. However, the mechanism mediating TNF-induced synovioblast survival versus cell death in RA is not fully understood. Our objective was to study the role of CD147 in TNF downstream pathway preference in RA synovioblasts. We found that overexpressing TNF in synovial tissue did not increase the apoptotic level and, in vitro, TNF-induced mild synovioblast apoptosis and promoted IL-6 secretion. CD147, which was highly expressed in rheumatoid arthritis synovial fibroblasts (RASFs), increased the resistance of synovioblasts to apoptosis under TNF stimulation. Downregulating CD147 both increased the apoptotic rate and inhibited IκB kinase (IKK)/IκB/NF-κB pathway-dependent proinflammatory cytokine secretion. Further, we determined that it was the extracellular portion of CD147 and not the intracellular portion that was responsible for synovioblast apoptosis resistance. CD147 monoclonal antibody inhibited TNF-induced proinflammatory cytokine production but had no effect on apoptotic rates. Thus, our study indicates that CD147 is resistant to TNF-induced apoptosis by promoting IKK/IκB/NF-κB pathway, and the extracellular portion of CD147 is the functional region.
  
  
  CONCLUSIONS
  CD147 inhibits TNF-stimulated RASF apoptosis. CD147 knockdown decreases IKK expression and inhibits NF-κB-related cytokine secretion. CD147's extracellular portion is responsible for apoptosis resistance. CD147 antibody inhibits TNF-related cytokine secretion without additional apoptosis.
authors: Department of Clinical Immunology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China.|Cell Engineering Research Center & Department of Cell Biology, Fourth Military Medical University, 17 West Changle Road, Xi'an, 710032, China.
authors: Yue
authors: Y
authors: Zhai
authors: Cell Engineering Research Center & Department of Cell Biology, Fourth Military Medical University, 17 West Changle Road, Xi'an, 710032, China.
authors: Bo
authors: B
authors: Wu
authors: Department of Clinical Immunology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China.
authors: Jia
authors: J
authors: Li
authors: Cell Engineering Research Center & Department of Cell Biology, Fourth Military Medical University, 17 West Changle Road, Xi'an, 710032, China.
authors: Xi-ying
authors: XY
authors: Yao
authors: Department of Clinical Immunology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China. zhuping@fmmu.edu.cn.
authors: Ping
authors: P
authors: Zhu
authors: Cell Engineering Research Center & Department of Cell Biology, Fourth Military Medical University, 17 West Changle Road, Xi'an, 710032, China. zhinanchen@fmmu.edu.cn.
authors: Zhi-nan
authors: ZN
authors: Chen
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010003:Osteoarthritis / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C497886:BSG protein, human; D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D051926:Basigin; D051550:I-kappa B Kinase
keywords: Apoptosis; CD147; NF-κB; Rheumatoid arthritis synovial fibroblast; TNF