Enhanced expression of MafB inhibits macrophage apoptosis induced by cigarette smoke exposure.
In the lungs of smokers, oxidative stress rises due to increase of free radicals and oxidants, including lipid peroxide (LPO). The functions of alveolar macrophages (AMs) are altered in such an environment, and their survival is prolonged against toxicities of cigarette smoke (CS) by an unknown mechanism. Whereas functions of AMs are potentially regulated by various transcriptional factors, their expressions and roles in smoking individuals have not been elucidated. Therefore, we investigated their expressions using murine model of CS exposure. Eight-week-old male B6C3F1 mice were whole-bodily exposed to CS (2 cigarettes/mouse/day, 5 d/wk) for 6 mo. Development of pulmonary emphysema in 6-mo CS-exposed mice was confirmed by a morphometric analysis. Among the transcriptional factors investigated, only MafB was upregulated in AMs from CS-exposed mice. DNA binding capacity of MafB for Maf recognition element was also increased in AMs from those mice. LPO was increased significantly in the lungs of CS-exposed mice. Because the end product of LPO, 4-hydroxy-2-nonenal, enhanced MafB expression and its transcriptional activity in a cultured macrophage cell line, LPO-related oxidative stress was suggested to be involved in the mechanism of MafB expression in CS-exposed lung. Furthermore, we established a macrophage cell line that can overexpress MafB and thereby clarify the role of MafB. Forced expression of MafB heightened cell viability and attenuated the occurrence of apoptosis in cells treated with CS-extract. These results suggest that enhanced MafB expression by oxidative stress inhibits AM cell death and prolongs their survival in the CS-exposed lung.
Machiya
Jun-Ichi
J
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Shibata
Yoko
Y
Yamauchi
Keiko
K
Hirama
Noriyuki
N
Wada
Toshihiro
T
Inoue
Sumito
S
Abe
Shuichi
S
Takabatake
Noriaki
N
Sata
Makoto
M
Kubota
Isao
I
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D051258:MafB Transcription Factor / Q000378:metabolism*; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D000447:Aldehydes; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D012906:Smoke; D014157:Transcription Factors; C027576:4-hydroxy-2-nonenal