Carbocisteine reduces virus-induced pulmonary inflammation in mice exposed to cigarette smoke

Yuichi Yageta, Yukio Ishii, Yuko Morishima, Satoshi Ano, Shigeo Ohtsuka, Masashi Matsuyama, Kaoru Takeuchi, Ken Itoh, Masayuki Yamamoto, Nobuyuki Hizawa

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Carbocisteine (S-CMC) inhibits viral infection and prevents acute exacerbation of chronic obstructive pulmonary disease. We recently demonstrated the protective effects of NF-E2-related 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 g glutamyl cysteine synthetase and heme oxigenase-1, were enhanced in a dosedependent 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.

Original languageEnglish
Pages (from-to)963-973
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Volume50
Issue number5
DOIs
Publication statusPublished - 2014 May

Keywords

  • Carbocisteine
  • Chronic obstructive pulmonary disease exacerbation
  • Influenza A virus
  • Macrophages
  • NF-E2-related factor 2

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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