title: CD97/ADGRE5 Inhibits LPS Induced NF-κB Activation through PPAR-γ Upregulation in Macrophages.
abstract: CD97/ADGRE5 protein is predominantly expressed on leukocytes and belongs to the EGF-TM7 receptors family. It mediates granulocytes accumulation in the inflammatory tissues and is involved in firm adhesion of PMNC on activated endothelial cells. There have not been any studies exploring the role of CD97 in LPS induced NF-κB activation in macrophages. Therefore, we first measured the CD97 expression in LPS treated human primary macrophages and subsequently analyzed the levels of inflammatory factor TNF-α and transcription factor NF-κB in these macrophages that have been manipulated with either CD97 knockdown or overexpression. We found that a reported anti-inflammatory transcription factor, PPAR-γ, was involved in the CD97 mediated NF-κB suppression. Furthermore, by immunofluorescence staining, we established that CD97 overexpression not only inhibited LPS induced p65 expression in the nucleus but also promoted the PPAR-γ expression. Moreover, using CD97 knockout THP-1 cells, we further demonstrated that CD97 promoted PPAR-γ expression and decreased LPS induced NF-κB activation. In conclusion, CD97 plays a negative role in LPS induced NF-κB activation and TNF-α secretion, partly through PPAR-γ upregulation.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Zewei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: C412456:ADGRE2 protein, human; C095004:ADGRE5 protein, human; D015703:Antigens, CD; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D043562:Receptors, G-Protein-Coupled