The Anti-inflammatory Mechanism of Heme Oxygenase-1 Induced by Hemin in Primary Rat Alveolar Macrophages

• DOI: 10.1007/s10753-011-9415-4
• Publication Date: 2011-12-12T10:46:18Z
• Authors: Chen Hualin; Xu Wenli; Liu Dapeng; Li Xijing; Pan Xiuhua; Pang Qingfeng
• Keywords: Inflammation; Lipopolysaccharides; 0303 health sciences; Arginase; Pyridines; Anti-Inflammatory Agents, Non-Steroidal; Imidazoles; Nitric Oxide Synthase Type II; Protoporphyrins; Lung Injury; Nitric Oxide; Interleukin-10; Rats; 3. Good health; 03 medical and health sciences; Phagocytosis; Macrophages, Alveolar; Animals; Hemin; Inflammation Mediators; Lung; Cells, Cultured; Heme Oxygenase-1

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.