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

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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.

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Acknowledgments

This work was supported by the following grant the Priority Academic Program Development of Jiangsu Higher Education Institutions, Peak of the six personnel in Jiangsu Province, and Jiangsu Province Graduate Education Innovation project no. CX09S_035Z and Xuzhou Medical College president’s fund (no. 09KJZ07).

Conflict of Interest

All of the authors declared that there was not any actual or potential conflict of interest in this paper.

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Correspondence to Pang Qingfeng.

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Hualin, C., Wenli, X., Dapeng, L. et al. The Anti-inflammatory Mechanism of Heme Oxygenase-1 Induced by Hemin in Primary Rat Alveolar Macrophages. Inflammation 35, 1087–1093 (2012). https://doi.org/10.1007/s10753-011-9415-4

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