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We recently demonstrated the protective effects of NF-E2\u2013related factor (Nrf) 2 against influenza virus (FluV)-induced pulmonary inflammation in mice exposed to cigarette smoke (CS). In our current study, we investigated the effects of S-CMC on Nrf2 activation in cultured macrophages, and in mice infected with influenza after exposure to CS. Nuclear translocation of Nrf2 and the expression of Nrf2-targeted antioxidant genes, such as heavy and light subunits of \u03b3 glutamyl cysteine synthetase and heme oxigenase-1, were enhanced in a dose-dependent manner after treatment with S-CMC in peritoneal and alveolar macrophages of wild-type mice, but not in those of Nrf2-deficient mice. Nuclear translocation of Nrf2 in macrophages was inhibited by the phosphatidylinositol 3-kinase inhibitor, LY294002. Phosphorylated Akt, Nrf2, and heme oxigenase-1 were induced in the alveolar macrophages of the lungs in wild-type mice after S-CMC administration. The extent of oxidative stress, inflammatory cell infiltration, pulmonary edema, and goblet cell hyperplasia was suppressed by S-CMC administration in the lungs of wild-type mice after exposure to both CS and FluV. Our findings suggest that S-CMC reduces pulmonary inflammation and mucus overproduction in mice exposed to CS after infection with FluV via the activation of Nrf2.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0292oc","type":"journal-article","created":{"date-parts":[[2013,12,4]],"date-time":"2013-12-04T12:39:17Z","timestamp":1386160757000},"page":"963-973","source":"Crossref","is-referenced-by-count":21,"title":["Carbocisteine Reduces Virus-Induced Pulmonary Inflammation in Mice Exposed to Cigarette Smoke"],"prefix":"10.1093","volume":"50","author":[{"given":"Yuichi","family":"Yageta","sequence":"first","affiliation":[{"name":"Departments of Respiratory Medicine and"},{"name":"Discovery Research Laboratories, Kyorin Pharmaceutical Company, Limited, Tochigi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Ishii","sequence":"additional","affiliation":[{"name":"Departments of Respiratory Medicine 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