Heme oxygenase-1 attenuates inflammation and oxidative damage in a rat model of smoke-induced emphysema

Wei,Jingjing; Fan,Guoquan; Zhao,Hui; Li,Jianqiang

doi:10.3892/ijmm.2015.2353

Heme oxygenase-1 attenuates inflammation and oxidative damage in a rat model of smoke-induced emphysema

Authors:
- Jingjing Wei
- Guoquan Fan
- Hui Zhao
- Jianqiang Li
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Affiliations: Department of Pediatrics, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Critical Care and Pulmonary Medicine, Shanxi Medical University Second Hospital, Taiyuan, Shanxi 030001, P.R. China
Published online on: September 22, 2015 https://doi.org/10.3892/ijmm.2015.2353
Pages: 1384-1392

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Abstract

Emphysema is a serious disease of the respiratory system and is associated with inflammation and oxidative stress. Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in heme biosynthesis, exerts potent anti-inflammatory, antioxidant, anti-apoptotic and anti‑proliferative effects in various diseases. In the present study, we examined the effects of HO-1 on smoke‑induced emphysema, as well as the underlying mechanisms in a rat model of smoke-induced emphysema. Rats were either exposed to cigarette smoke or sham‑exposed for 20 weeks to establish the model of smoke-induced emphysema. The rats were subcutaneously injected with protoporphyrin IX [tin-protoporphyrin IX (SnPP) or ferriprotoporphyrin IX chloride (hemin)] during this period to examine the protective effects of HO-1. Subsequently, the development of emphysema, inflammatory cells, the levels of inflammatory mediators, particularly interleukin (IL)-17, tumor necrosis factor (TNF)‑α, monocyte chemotactic protein‑1 [MCP‑1, also known as chemokine (C-C motif) ligand 2 (CCL2)], IL-8 [also known as chemokine (C-X-C motif) ligand 8 (CXCL8)], macrophage inflammatory protein‑2α [MIP-2α, also known as chemokine (C-X-C motif) ligand 2 (CXCL2)] and IL-10, as well as the malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) content were determined. Exposure to smoke increased the total cell, neutrophil and macrophage counts in the bronchoalveolar lavage fluid (BALF). It also increased the levels of the inflammatory mediators, IL-17, TNF-α, MCP-1, IL-8 and MIP-2α, as well as the MDA content and induced emphysema. Treatment with hemin upregulated HO-1 expression and attenuated the development of smoke-induced emphysema by reducing inflammatory cell infiltration, decreasing the levels of inflammatory mediators and attenuating oxidative damage, to a certain extent. In conclusion, our findings demonstrate that HO-1 exerts anti-inflammatory and antioxidant effects, thus attenuating the development of smoke-induced emphysema.

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