Compounds in cigarette smoke induce EGR1 expression via the AHR, resulting in apoptosis and COPD

Author:

Hattori Naoko123,Nakagawa Takeya12,Yoneda Mitsuhiro12,Hayashida Hiromi12,Nakagawa Kaori12,Yamamoto Kazuo4,Htun Myo Win15,Shibata Yasuaki13,Koji Takehiko15,Ito Takashi12

Affiliation:

1. Nagasaki University Graduate School of Biomedical Sciences , Nagasaki 852-8523, Japan

2. Nagasaki University School of Medicine Department of Biochemistry, , Nagasaki 852-8523, Japan

3. Nagasaki University Graduate School of Biomedical Sciences Department of Dermatology, , Nagasaki 852-8523, Japan

4. Nagasaki University School of Medicine Biomedical Research Support Center, , Nagasaki 852-8523, Japan

5. Nagasaki University School of Medicine Department of Histology and Cell Biology, , Nagasaki 852-8523, Japan

Abstract

Abstract Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide, and pulmonary epithelial cell apoptosis is regarded as one of the most important factors in its pathogenesis. Here, we examined the molecular mechanisms of apoptosis caused by cigarette smoke (CS). In the normal bronchial epithelium cell line BEAS-2B, a CS extract markedly induced apoptosis together with transient early growth response 1 (EGR1) protein expression, which is activated over time via the aryl hydrocarbon receptor (AHR). The CS extract–induced apoptosis decreased cell count of BEAS-2B cells and was significantly reversed by knockdown of either EGR1 or AHR. In vivo, the CS extract caused alveolar wall destruction, mimicking COPD, 1 week after intrathoracic injection. Bronchoalveolar lavage fluid (BALF) from the CS extract–treated mice contained massive numbers of apoptotic epithelial cells. Furthermore, it was found that aminoanthracene induced EGR1 expression and cell apoptosis. By contrast, the AHR antagonist stemregenin 1 (SR1) restored apoptosis upon CS treatment. These results suggest that aryl hydrocarbons, such as aminoanthracene, induce EGR1 expression via the AHR, resulting in cell apoptosis and that this can be prevented by administration of an antagonist of AHR.

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Biochemistry,General Medicine

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