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Cigarette Smoke Exposure Attenuates Cytokine Production by Mouse Alveolar Macrophages
Abstract
Alveolar macrophages (aMϕs) play a central role in respiratory host defense by sensing microbial antigens and initiating immune-inflammatory responses early in the course of an infection. The purpose of this study was to investigate the effect of cigarette smoke exposure on aMϕs after stimulation of innate pattern recognition receptors (PRRs) in a murine model. To accomplish this, C57BL/6 mice were exposed for 8 weeks using two models of cigarette smoke exposure, nose-only or whole-body exposure, and aMϕs isolated from the bronchoalveolar lavage. After stimulation of aMϕs with pI:C, a mimic of viral replication, and bacterial cell-wall constituent LPS, aMϕs from cigarette smoke–exposed mice produced significantly attenuated levels of the inflammatory cytokines TNF-α and IL-6, and the chemokine RANTES. This attenuation was specific to the aMϕ compartment, and not related to changes in aMϕ viability or expression of Toll-like receptor (TLR)3 or TLR4 between groups. Furthermore, aMϕs from smoke-exposed mice had decreased cytokine RNA as compared with aMϕs from sham-exposed mice. Mechanistically, this was associated with decreased nuclear translocation of the proinflammatory transcription factor NF-κB, and increased activator protein-1 nuclear translocation, in aMϕs from smoke-exposed mice. Attenuated cytokine production was reversible after smoking cessation. Cigarette smoke exposure also attenuated TNF-α production after stimulation with nucleotide-oligomerization domain–like receptor agonists, showing that the effect applies more broadly to other PRR pathways. Our data demonstrate that cigarette smoke exposure attenuates aMϕ responses after innate stimulation, including pathways typically associated with bacterial and viral infections.
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“This is consistent with the generally accepted notion that cigarette smoking is, in general, immunosuppressive50.”
From The effect of smoking on chronic inflammation, immune function and blood cell composition (2020) · cites this paper as [50]
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Negative regulation of Toll-like receptor-mediated immune responses
Liew, F. Y., Xu, D., Brint, E. K., & O'Neill, L. A. J. (2005) · Nature Reviews Immunology · doi:10.1038/nri1630 · Cited by 1,509
Infections and Airway Inflammation in Chronic Obstructive Pulmonary Disease Severe Exacerbations
Papi, A., Bellettato, C. M., Braccioni, F., Romagnoli, M., Casolari, P., Caramori, G., Fabbri, L. M., & Johnston, S. L. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200506-859oc · Cited by 1,072
Alveolar Macrophage in the Driver's Seat
Lambrecht, B. N. (2006) · Immunity · doi:10.1016/j.immuni.2006.03.008 · Cited by 242
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Cited by
The effect of smoking on chronic inflammation, immune function and blood cell composition
Elisia, I., Lam, V., Cho, B., Hay, M., Li, M. Y., Yeung, M., Bu, L., Jia, W., Norton, N., Lam, S., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-76556-7 · Cited by 263
Smoking-induced iron dysregulation in the lung
Zhang, W. Z., Butler, J. J., & Cloonan, S. M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.07.024 · Cited by 62
Metadata
- Authors
- Gaschler, G. J., Zavitz, C. C. J., Bauer, C. M. T., Skrtic, M., Lindahl, M., Robbins, C. S., Chen, B., & Stämpfli, M. R.
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-02-01
- Volume
- 38
- Issue
- 2
- Pages
- 218-226
- ISSN
- 1044-1549
- 1535-4989
- Cited by
- 94
- References
- 3
- Language
- en
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