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
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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.
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页码：240 / 246
页数：6
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