title: IRS-2 deficiency in macrophages promotes their accumulation in the vascular wall.
abstract: The aim of this study was to investigate the role of insulin receptor substrate-2 (IRS-2) mediated signal in macrophages on the accumulation of macrophages in the vascular wall. Mice transplanted with IRS-2(-/-) bone marrow, a model of myeloid cell restricted defect of IRS-2, showed accumulation of monocyte chemoattractant protein-1-expressing macrophages in the vascular wall. Experiments using cultured peritoneal macrophages showed that IRS-2-mediated signal pathway stimulated by physiological concentrations of insulin, not by IL-4, contributed to the suppression of monocyte chemoattractant protein-1 expression induced by lipopolysaccharide. Our data indicated that IRS-2 deficiency in macrophages enhanced their accumulation in the vascular wall accompanied by increased expression of proinflammatory mediators in macrophages. These results suggest a role for insulin resistance in macrophages in early atherosclerogenesis.
authors.affiliation: Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mita
authors.forename: Kosuke
authors.initials: K
authors.lastname: Azuma
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Goto
authors.forename: Wen Long
authors.initials: WL
authors.lastname: Jin
authors.forename: Masayuki
authors.initials: M
authors.lastname: Arakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomiyama
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000276:immunology*; D016026:Bone Marrow Transplantation; D018932:Chemokine CCL2 / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000172:deficiency* / Q000235:genetics; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse