title: Heme oxygenase-1 and anti-inflammatory M2 macrophages.
abstract: Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting enzymatic step of heme degradation and produces carbon monoxide, free iron, and biliverdin. HO-1, a stress-inducible protein, is induced by various oxidative and inflammatory signals. Consequently, HO-1 expression has been regarded as an adaptive cellular response against inflammatory response and oxidative injury. Although several transcriptional factors and signaling cascades are involved in HO-1 regulation, the two main pathways of Nrf2/Bach1 system and IL-10/HO-1 axis exist in monocyte/macrophage. Macrophages are broadly divisible into two groups: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. More recently, several novel macrophage subsets have been identified including Mhem, Mox, and M4 macrophages. Of these, M2 macrophages, Mhem, and Mox are HO-1 highly expressing macrophages. HO-1 has been recognized as having major immunomodulatory and anti-inflammatory properties, which have been demonstrated in HO-1 deficient mice and human cases of genetic HO-1 deficiency. However, the mechanism underlying the immunomodulatory actions of HO-1 remains poorly defined. This review specifically addresses macrophage polarization. The present current evidence indicates that HO-1 induction mediated by multiple pathways can drive the phenotypic shift to M2 macrophages and suggests that HO-1 induction in macrophages is a potential therapeutic approach to immunomodulation in widely diverse human diseases.
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan. Electronic address: ynaito@koto.kpu-m.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan; Department of Food Factor Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Higashimura
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000276:immunology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000276:immunology
chemical_list: C102108:BACH1 protein, human; C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; C508609:IL10 protein, human; C556062:IL10 protein, mouse; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D016753:Interleukin-10; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Heme oxygenase; Inflammation; Macrophage; Polarization