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Nat Med. 2002 Mar;8(3):240-6.

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

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1
Graduate Institute of Life Sciences, National Defense Medical Center, and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.

Abstract

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-alpha 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.

PMID:
11875494
DOI:
10.1038/nm0302-240
[Indexed for MEDLINE]

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