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Heme oxygenase-1, a potential biomarker of chronic silicosis, attenuates silica-induced lung injury.

Authors: Sato, T  Takeno, M  Honma, K  Yamauchi, H  Saito, Y  Sasaki, T  Morikubo, H  Nagashima, Y  Takagi, S  Yamanaka, K  Kaneko, T  Ishigatsubo, Y 
Citation: Sato T, etal., Am J Respir Crit Care Med. 2006 Oct 15;174(8):906-14. Epub 2006 Jul 20.
Pubmed: (View Article at PubMed) PMID:16858012
DOI: Full-text: DOI:10.1164/rccm.200508-1237OC

RATIONALE: Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has antioxidative, antiapoptotic, and antiinflammatory activities. We examined whether HO-1 might be involved in silicosis. OBJECTIVES: To investigate whether HO-1 can reduce silicosis in mice and humans. METHODS AND MEASUREMENTS: Silicosis was studied using a murine model, and in 46 male patients. Serum HO-1 and 8-hydroxydeoxyguanosine (a marker of oxidative stress) were measured by enzyme-linked immunosorbent assay. Levels of HO-1 were measured by immunohistochemistry and immunoblotting. MAIN RESULTS: Serum HO-1 levels were significantly elevated in patients with silicosis compared with age-matched control subjects or patients with chronic obstructive pulmonary disease. Serum HO-1 levels also correlated inversely with serum 8-hydroxydeoxyguanosine levels and positively with vital capacity and forced expiratory volume in one second in patients with silicosis. HO-1 was present in the lungs of humans and mice with silicosis, especially at sites of silica particle deposition. In mice, silica exposure was associated with acute leukocyte infiltration, leading to development of silicotic lung lesions. The inflammation was suppressed by treatment with hemin, an inducer of HO-1, and enhanced by zinc protoporphyrin, an inhibitor of HO-1. CONCLUSIONS: Pulmonary HO-1 expression is increased in silicosis. HO-1 suppresses reactive oxygen species activity, and subsequent pathologic changes, thereby attenuating disease progression.


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RGD Object Information
RGD ID: 4145384
Created: 2010-11-02
Species: All species
Last Modified: 2010-11-02
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.