Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice

被引：0
作者：
Tzong-Shyuan Lee
Lee-Young Chau
机构：
[1] Graduate Institute of Life Sciences,
[2] National Defense Medical Center,undefined
[3] and Institute of Biomedical Sciences,undefined
[4] Academia Sinica,undefined
来源：
Nature Medicine | 2002年 / 8卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The mechanisms underlying the action of the potent anti-inflammatory interleukin-10 (IL-10) are poorly understood. Here we show that, in murine macrophages, IL-10 induces expression of heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, via a p38 mitogen-activated protein kinase-dependent pathway. Inhibition of HO-1 protein synthesis or activity significantly reversed the inhibitory effect of IL-10 on production of tumor necrosis factor-α induced by lipopolysaccharide (LPS). Additional experiments revealed the involvement of carbon monoxide, one of the products of HO-1-mediated heme degradation, in the anti-inflammatory effect of IL-10 in vitro. Induction of HO-1 by IL-10 was also evident in vivo. IL-10-mediated protection against LPS-induced septic shock in mice was significantly attenuated by cotreatment with the HO inhibitor, zinc protoporphyrin. The identification of HO-1 as a downstream effector of IL-10 provides new possibilities for improved therapeutic approaches for treating inflammatory diseases.
引用
收藏
页码：240 / 246
页数：6
相关论文
共 134 条
[11]  
Finbloom DS(1999)Cell biology of heme Am. J. Med. Sci. 318 241-256
[12]  
O'Farrell AM(2000)Heme oxygenase: colors of defense against cellular stress Am. J. Physiol. 279 L1029-1037
[13]  
Liu Y(2000)Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway Nature Med. 6 422-427
[14]  
Moore KW(1995)Interleukin-6 family of cytokines and gp130 Blood 86 1243-1254
[15]  
Mui AL-F(2001)IL-10 up-regulates macrophage expression of the S100 protein S100A8 J. Immunol. 166 6358-6366
[16]  
Riley JK(2001)Mammalian MAP kinase signaling cascades Nature 410 37-40
[17]  
Takeda K(2000)Hypoxia differentially regulates stress proteins in cultured cardiomyocytes: role of the p38 stress-activated kinase signaling cascade and relation to cytoprotection Cardiovas. Res. 46 139-150
[18]  
Akira S(2000)Nitric oxide induces heme oxygenase-1 via mitogen-activated protein kinases ERK and p38 Cell Mol. Biol. 46 609-617
[19]  
Schreiber RD(2000)Mechanism of heme oxygenase-1 gene activation by cadmium in MCF-7 mammary epithelial cells. Role of p38 kinase and Nrf2 transcription factor J. Biol. Chem. 275 27694-27702
[20]  
Crawley JB(2001)LPS induction of gene expression in human monocytes Cell Signal. 13 85-94
12345678910