title: The anti-inflammatory mechanism of heme oxygenase-1 induced by hemin in primary rat alveolar macrophages.
abstract: Alveolar macrophages (AMs) can initiate lung inflammation by producing pro-inflammatory cytokines and chemokines, but they participate actively in the prevention of inflammation during acute lung injury (ALI). Heme oxygenase-1 (HO-1) is mainly expressed in AMs and has anti-inflammatory properties in ALI, but the anti-inflammatory mechanisms of HO-1 are largely unknown. In this study, AMs were treated with saline, LPS (1 μg/ml), hemin (10 μM), zinc protoporphyrin (ZnPP; 10 μM, 1 h prior to LPS and hemin), SB203580 (10 μM, 1 h prior to LPS and hemin), or their combination up to 24 h. The specific HO-1 inhibitor ZnPP and SB203580 were used to inhibit the effects of HO-1 and the phosphorylated p38 mitogen-activated protein kinase (MAPK), respectively. The protein levels of HO-1 and p38 MAPK were analyzed by western blotting; arginase activity was measured in lysates obtained from cultured cells; nitric oxide production in the extracellular medium of AMs cultured for 24 h was monitored by assessing nitrite levels; the phagocytic ability of macrophage was measured by neutral red uptake. IL-10 of culture supernatants in AMs was determined by enzyme-linked immunosorbent assay. The results indicated that HO-1 induced by hemin increased arginase activity and phagocytic ability and decreased iNOS activity via p38 MAPK pathway in primary rat AMs. These changes and p38 MAPK may be the anti-inflammatory mechanism of HO-1 induced by hemin in primary rat AMs.
authors.affiliation: Jiangsu Province Institute of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hualin
authors.forename: Xu
authors.initials: X
authors.lastname: Wenli
authors.forename: Liu
authors.initials: L
authors.lastname: Dapeng
authors.forename: Li
authors.initials: L
authors.lastname: Xijing
authors.forename: Pan
authors.initials: P
authors.lastname: Xiuhua
authors.forename: Pang
authors.initials: P
authors.lastname: Qingfeng
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001119:Arginase / Q000378:metabolism; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D055370:Lung Injury / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010587:Phagocytosis; D011524:Protoporphyrins / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011524:Protoporphyrins; D011725:Pyridines; D016753:Interleukin-10; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D006427:Hemin; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; D001119:Arginase; C093642:SB 203580