tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2013 Dec 4. [Epub ahead of print]
Carbocisteine Reduces Viral-Induced Pulmonary Inflammation in Mice Exposed to Cigarette Smoke.
Yageta Y, Ishii Y, Morishima Y, Ano S, Ohtsuka S, Matsuyama M, Takeuchi K, Itoh K, Yamamoto M, Hizawa N.
Source
Development Research Laboratories, Kyorin Pharmaceutical Co., Ltd, Tokyo, Japan ; yuuichi.yageta@mb.kyorin-pharm.co.jp.
Abstract
Carbocisteine inhibits viral infection and prevents acute exacerbation of chronic obstructive pulmonary disease. We recently demonstrated the protective effects of Nrf2 against influenza virus-induced pulmonary inflammation in mice exposed to cigarette smoke. In our current study, we investigated the effects of carbocisteine on Nrf2 activation in cultured macrophages, and in mice infected with influenza following exposure to cigarette smoke. Nuclear translocation of Nrf2 and the expression of Nrf2-targeted anti-oxidant genes, such as heavy and light subunits of gamma glutamyl cysteine synthetase, and heme oxigenase-1, were enhanced in a dose-dependent manner following treatment with carbocisteine 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 carbocisteine administration. The extent of oxidative stress, inflammatory cell infiltration, pulmonary edema, and goblet cell hyperplasia was suppressed by carbocisteine administration in the lungs of wild-type mice after exposure to both cigarette smoke and influenza virus. Our findings suggest that carbocisteine reduces pulmonary inflammation and mucus overproduction in mice exposed to cigarette smoke following infection with influenza virus via the activation of Nrf2.
PMID:
24303786
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24303786
Carbocisteine Reduces Viral-Induced Pulmonary Inflammation in Mice Exposed to Cigarette Smoke.
Yageta Y, Ishii Y, Morishima Y, Ano S, Ohtsuka S, Matsuyama M, Takeuchi K, Itoh K, Yamamoto M, Hizawa N.
Source
Development Research Laboratories, Kyorin Pharmaceutical Co., Ltd, Tokyo, Japan ; yuuichi.yageta@mb.kyorin-pharm.co.jp.
Abstract
Carbocisteine inhibits viral infection and prevents acute exacerbation of chronic obstructive pulmonary disease. We recently demonstrated the protective effects of Nrf2 against influenza virus-induced pulmonary inflammation in mice exposed to cigarette smoke. In our current study, we investigated the effects of carbocisteine on Nrf2 activation in cultured macrophages, and in mice infected with influenza following exposure to cigarette smoke. Nuclear translocation of Nrf2 and the expression of Nrf2-targeted anti-oxidant genes, such as heavy and light subunits of gamma glutamyl cysteine synthetase, and heme oxigenase-1, were enhanced in a dose-dependent manner following treatment with carbocisteine 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 carbocisteine administration. The extent of oxidative stress, inflammatory cell infiltration, pulmonary edema, and goblet cell hyperplasia was suppressed by carbocisteine administration in the lungs of wild-type mice after exposure to both cigarette smoke and influenza virus. Our findings suggest that carbocisteine reduces pulmonary inflammation and mucus overproduction in mice exposed to cigarette smoke following infection with influenza virus via the activation of Nrf2.
PMID:
24303786
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24303786