title: Resistin-like molecule β is abundantly expressed in foam cells and is involved in atherosclerosis development.
abstract: OBJECTIVE
  Resistin-like molecule (RELM) β is a secretory protein homologous to resistin and reportedly contributes to local immune response regulation in gut and bronchial epithelial cells. However, we found that activated macrophages also express RELMβ and thus investigated the role of RELMβ in the development of atherosclerosis.
  
  
  RESULTS
  It was demonstrated that foam cells in atherosclerotic lesions of the human coronary artery abundantly express RELMβ. RELMβ knockout ((-/-)) and wild-type mice were mated with apolipoprotein E-deficient background mice. RELMβ(-/-) apolipoprotein E-deficient mice exhibited less lipid accumulation in the aortic root and wall than RELMβ(+/+) apolipoprotein E-deficient mice, without significant changes in serum lipid parameters. In vitro, RELMβ(-/-) primary cultured peritoneal macrophages (PCPMs) exhibited weaker lipopolysaccharide-induced nuclear factor-κB classical pathway activation and inflammatory cytokine secretion than RELMβ(+/+), whereas stimulation with RELMβ upregulated inflammatory cytokine expressions and increased expressions of many lipid transporters and scavenger receptors in PCPMs. Flow cytometric analysis revealed inflammatory stimulation-induced RELMβ in F4/80(+) CD11c(+) PCPMs. In contrast, the expressions of CD11c and tumor necrosis factor were lower in RELMβ(-/-) PCPMs, but both were restored by stimulation with recombinant RELMβ.
  
  
  CONCLUSIONS
  RELMβ is abundantly expressed in foam cells within plaques and contributes to atherosclerosis development via lipid accumulation and inflammatory facilitation.
authors.affiliation: Department of Internal Medicine, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Masamichi
authors.initials: M
authors.lastname: Okubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: Haruya
authors.initials: H
authors.lastname: Ono
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fukushima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kamata
authors.forename: Fusanori
authors.initials: F
authors.lastname: Nishimura
authors.forename: Takako
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Sakura
authors.initials: S
authors.lastname: Kushiyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Iizuka
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taki
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Encinas
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawazu
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D039521:CD11c Antigen / Q000378:metabolism; D002460:Cell Line; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D005487:Foam Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006729:Hormones, Ectopic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D061251:Primary Cell Culture; D014657:Vasculitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D039521:CD11c Antigen; D005227:Fatty Acids; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; C486574:RETNLB protein, human; C486522:Retnlb protein, mouse
keywords: atherosclerosis; inflammation; macrophage