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

被引:52
作者
Chen Hualin [2 ]
Xu Wenli [2 ]
Liu Dapeng [2 ]
Li Xijing [1 ]
Pan Xiuhua [1 ]
Pang Qingfeng [1 ]
机构
[1] Xuzhou Med Coll, Dept Pathophysiol, Xuzhou 221002, Jiangsu, Peoples R China
[2] Xuzhou Med Coll, Jiangsu Prov Inst Anesthesiol, Xuzhou 221002, Jiangsu, Peoples R China
关键词
alveolar macrophages; heme oxygenase-1; anti-inflammatory; p38; MAPK; NITRIC-OXIDE SYNTHASE; IL-10; PRODUCTION; PROTEIN-KINASE; LUNG; EXPRESSION; LIPOPOLYSACCHARIDE; CELLS; ARGINASE; INJURY; INHIBITION;
D O I
10.1007/s10753-011-9415-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 mu g/ml), hemin (10 mu M), zinc protoporphyrin (ZnPP; 10 mu M, 1 h prior to LPS and hemin), SB203580 (10 mu M, 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.
引用
收藏
页码:1087 / 1093
页数:7
相关论文
共 38 条
[1]   Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages [J].
Ashino, Takashi ;
Yamanaka, Rieko ;
Yamamoto, Masayuki ;
Shimokawa, Hiroaki ;
Sekikawa, Kenji ;
Iwakura, Yoichiro ;
Shioda, Seiji ;
Numazawa, Satoshi ;
Yoshida, Takemi .
MOLECULAR IMMUNOLOGY, 2008, 45 (07) :2106-2115
[2]   Induction of ferritin and heme oxygenase-1 by endotoxin in the lung [J].
Carraway, MS ;
Ghio, AJ ;
Taylor, JL ;
Piantadosi, CA .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1998, 275 (03) :L583-L592
[3]   Expression of heme oxygenase-1 in the lung in chronic hypoxia [J].
Carraway, MS ;
Ghio, AJ ;
Carter, JD ;
Piantadosi, CA .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 278 (04) :L806-L812
[4]   LPS induces IL-10 production by human alveolar macrophages via MAPKinases- and Sp1-dependent mechanisms [J].
Chanteux, Hugues ;
Guisset, Amelie C. ;
Pilette, Charles ;
Sibille, Yves .
RESPIRATORY RESEARCH, 2007, 8 (1)
[5]   Effects of the acid polysaccharide fraction isolated from a cultivated Cordyceps sinensis on macrophages in vitro [J].
Chen, Weixia ;
Zhang, Weiyun ;
Shen, Wenbin ;
Wang, Kongcheng .
CELLULAR IMMUNOLOGY, 2010, 262 (01) :69-74
[6]  
Deshane J, 2005, ACTA BIOCHIM POL, V52, P273
[7]   Differential regulation of cardiac heme oxygenase-1 and vascular endothelial growth factor mRNA expressions by hemin, heavy metals, heat shock and anoxia [J].
EyssenHernandez, R ;
Ladoux, A ;
Frelin, C .
FEBS LETTERS, 1996, 382 (03) :229-233
[8]   Inducers of heme oxygenase-1 [J].
Ferrandiz, M. L. ;
Devesa, I. .
CURRENT PHARMACEUTICAL DESIGN, 2008, 14 (05) :473-486
[9]   Interleukin-4 and dexamethasone counterregulate extracellular matrix remodelling and phagocytosis in type-2 macrophages [J].
Gratchev, A ;
Kzhyshkowska, J ;
Utikal, J ;
Goerdt, S .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2005, 61 (01) :10-17
[10]   A MAP KINASE TARGETED BY ENDOTOXIN AND HYPEROSMOLARITY IN MAMMALIAN-CELLS [J].
HAN, J ;
LEE, JD ;
BIBBS, L ;
ULEVITCH, RJ .
SCIENCE, 1994, 265 (5173) :808-811