title: HDL/apolipoprotein A-I binds to macrophage-derived progranulin and suppresses its conversion into proinflammatory granulins.
abstract: OBJECTIVE
  HDL has anti-inflammatory effects on macrophages, although the mechanism of action remains unclear. We hypothesized that HDL suppresses the conversion of macrophage-secreted factors into proinflammatory factors via binding, and tried to identify the factor that could form a complex with HDL and/or apolipoprotein (apo) A-I.
  
  
  RESULTS
  In conditioned media obtained from human monocyte-derived macrophages, we found an apo A-I binding protein and identified the protein as progranulin/proepithelin/acrogranin/PCDGF. Co-immunoprecipitation analysis showing that progranulin binds and forms a complex with apo A-I and the presence of progranulin in the HDL fraction in the sera indicated that progranilin is a novel apolipoprotein. Conditioned media of HEK293 cells transfected with progranulin augmented the expression of TNF-alpha and IL-1-beta on macrophages, but these effects of progranulin were inhibited by co-incubation with HDL or apo A-I. Anti-progranulin antibodies also reduced the expression of TNF-alpha and IL-1-beta on macrophages. Granulins as conversion products derived from progranilin increased TNF-alpha and IL-1-beta expression and the effects were not suppressed by HDL.
  
  
  CONCLUSIONS
  Our results suggest that the anti-inflammatory effects of HDL on macrophages might be due to suppression of the conversion of progranulin into proinflammatory granulins by forming a complex.
authors.affiliation: Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe 650-0047, Japan.
authors.forename: Hanayuki
authors.initials: H
authors.lastname: Okura
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohama
authors.forename: Ayami
authors.initials: A
authors.lastname: Saga
authors.forename: Aya
authors.initials: A
authors.lastname: Yamamoto-Kakuta
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hamada
authors.forename: Nagako
authors.initials: N
authors.lastname: Sougawa
authors.forename: Reiko
authors.initials: R
authors.lastname: Ohyama
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
mesh_terms: D000893:Anti-Inflammatory Agents; D016632:Apolipoprotein A-I / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D006801:Humans; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D008075:Lipoproteins, HDL; D008264:Macrophages / Q000378:metabolism; D019899:Paracrine Communication; D000077153:Progranulins; D011485:Protein Binding
chemical_list: D000893:Anti-Inflammatory Agents; D016632:Apolipoprotein A-I; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL; D000077153:Progranulins