title: Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.
abstract: Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis.
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China; Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Jie-jie
authors.initials: JJ
authors.lastname: Geng
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Li-na
authors.initials: LN
authors.lastname: Chen
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Jin-lin
authors.initials: JL
authors.lastname: Miao
authors.affiliation: Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Zhi-guang
authors.initials: ZG
authors.lastname: Fu
authors.affiliation: Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China. Electronic address: chcerc2@fmmu.edu.cn.
authors.forename: Zhi-nan
authors.initials: ZN
authors.lastname: Chen
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China. Electronic address: zhuping@fmmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D051926:Basigin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001761:Bleomycin / Q000633:toxicity; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C497887:Bsg protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D001761:Bleomycin; D051926:Basigin
keywords: CD147; Lung interstitial fibrosis; M1; M2; Macrophages; Th17