Journal
TOXICOLOGY LETTERS
Volume 270, Issue -, Pages 17-24Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2017.02.002
Keywords
Cigarette smoke; Activating transcription factor 3; Interleukin 6; Interleukin 8; Nuclear factor-kappa B
Categories
Funding
- National Natural Science Foundation of China [81170037, 81370126]
- National Clinical Research Center of China for Respiratory Disease
- Medical Science and Technology Plan Projects of Ningbo [2016A03]
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Airway and lung inflammation is a fundamental hallmark of chronic obstructive pulmonary disease (COPD). Activating transcription factor 3 (ATF3) has been reported to negatively regulate many pro inflammatory cytokines and chemokines. However, little is known about the impact of ATF3 on the inflammatory response of COPD. Since cigarette smoke (CS) is considered to be the most important risk factor in the etiology of COPD, we attempted to investigate the effects and molecular mechanisms of ATF3 in CS-induced inflammation. We observed an increase in the expression of ATF3 in the lung tissues of CS exposed mice and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. In vitro results indicated that ATF3 inhibition significantly increased the expression of proinflammatory cytokines interleukin 6 (IL6) and interleukin 8 (IL8) in CSE-stimulated HBE cells. Furthermore, in vivo data verified that CS induced inflammatory cell recruitment around the bronchus. In addition, neutrophil infiltration in bronchoalveolar lavage fluid (BALF) of CS-exposed Atf(3-/-) mice was markedly higher than in stimulated WT mice. Finally, ATF3 deficiency increased the in vitro and in vivo expression and phosphorylation of nuclear factor-kappa B (NF-kappa B), a positive mediator of inflammation. Thus, this study shows that ATF3 plays an important role in the negative regulation of CS-induced pro-inflammatory gene expression through downregulating NF-kappa B phosphorylation. (C) 2017 Elsevier B.V. All rights reserved.
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