Both reactive oxygen species and reactive nitrogen species participate in the redox-regulation of toluene diisocyanate-induced lung inflammation

• Main Authors: Pei-ChiLo, 羅姵淇
• Other Authors: Chi-Chang Shieh
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/83723738251111303352

碩士 === 國立成功大學 === 臨床醫學研究所 === 101 === Toluene diisocyanate (TDI) is an oxidizing chemical which induces occupational asthma. Workplace exposure to TDI leads to lung inflammation with distinctive leukocyte infiltration and nitric oxide (NO) production. Our previous research showed that leukocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is essential for inducing pulmonary inflammation with TDI. To clarify the role of the redox regulation in TDI-induced pulmonary inflammation, we investigated the redox regulation in wild type (WT) mice, NADPH oxidase subunit p47phox/ neutrophil cytosolic factor1 deficient mice (Ncf1-/-), inducible nitric oxide synthase (iNOS) deficient mice (Nos2-/-), and Ncf1 and Nos2 double gene-deficient mice (Ncf1-/- /Nos2-/-). Histopathological evaluation demonstrated more severe inflammatory cells infiltration around the bronchiole and capillary in WT than in Ncf1-/-, Nos2-/- , and Ncf1-/- /Nos2-/- mice after TDI exposure. TDI caused both oxidative and nitrosative stress, reflected by dramatically increased levels of the lipid peroxidation end product malindialdehyde (MDA), iNOS activation, NO production, and nitrotyrosine expression in WT mice, but not in Ncf1-/-, Nos2-/-, and Ncf1-/- /Nos2-/- mice. The expression of cytokines including interferon- (IFN-), IFN--induced protein 10 (IP-10), interleukin 2 (IL-2), IL-4, IL-5, IL-17, and tumor necrosis factor- (TNF-) significantly increased after TDI exposure in WT mice. However, high baseline iNOS expression and cytokine production before TDI stimulation were noted in Ncf1-/- mice. We hence conclude that both ROS and RNS participate in the redox-regulation of TDI-induced lung inflammation. Both ROS and RNS play important roles in lung inflammation because lacking of either leukocyte NADPH oxidase or iNOS lowered but did not completely abolish TDI-induced lung inflammation, whereas lacking of both genes prevented lung inflammation. These results suggest that ROS and RNS have individual and overlapping roles in TDI-induced occupational asthma.