Version 1
: Received: 22 March 2024 / Approved: 22 March 2024 / Online: 25 March 2024 (07:38:11 CET)
Version 2
: Received: 22 March 2024 / Approved: 25 March 2024 / Online: 25 March 2024 (08:49:57 CET)
How to cite:
Asare, P. F.; Hodge, G.; Ween, M.; Hamon, R.; Truong, T. T.; Jersmann, H.; Reynolds, P.; Hodge, S.; Tran, H. B. Double Targeting Inflammasome Activation and Accelerated Cellular Senescence in Alveolar Macrophages Exposed to Cigarette Smoke and COPD. Preprints2024, 2024031380. https://doi.org/10.20944/preprints202403.1380.v1
Asare, P. F.; Hodge, G.; Ween, M.; Hamon, R.; Truong, T. T.; Jersmann, H.; Reynolds, P.; Hodge, S.; Tran, H. B. Double Targeting Inflammasome Activation and Accelerated Cellular Senescence in Alveolar Macrophages Exposed to Cigarette Smoke and COPD. Preprints 2024, 2024031380. https://doi.org/10.20944/preprints202403.1380.v1
Asare, P. F.; Hodge, G.; Ween, M.; Hamon, R.; Truong, T. T.; Jersmann, H.; Reynolds, P.; Hodge, S.; Tran, H. B. Double Targeting Inflammasome Activation and Accelerated Cellular Senescence in Alveolar Macrophages Exposed to Cigarette Smoke and COPD. Preprints2024, 2024031380. https://doi.org/10.20944/preprints202403.1380.v1
APA Style
Asare, P. F., Hodge, G., Ween, M., Hamon, R., Truong, T. T., Jersmann, H., Reynolds, P., Hodge, S., & Tran, H. B. (2024). Double Targeting Inflammasome Activation and Accelerated Cellular Senescence in Alveolar Macrophages Exposed to Cigarette Smoke and COPD. Preprints. https://doi.org/10.20944/preprints202403.1380.v1
Chicago/Turabian Style
Asare, P. F., Sandra Hodge and Hai Bac Tran. 2024 "Double Targeting Inflammasome Activation and Accelerated Cellular Senescence in Alveolar Macrophages Exposed to Cigarette Smoke and COPD" Preprints. https://doi.org/10.20944/preprints202403.1380.v1
Abstract
We hypothesise that anti-inflammatory macrolides can alleviate both the NLRP3 inflammasome activation and accelerated senescence in alveolar macrophages in COPD and/or response to cigarette smoke. Lung tissues from COPD patients and mice chronically exposed to cigarette smoke, cultures of human primary alveolar macrophages and macrophages derived from blood (MDM) or THP-1 monocytes were analysed for markers of macrophage NLRP3 inflammasome activation and accelerated senescence using multifluorescence quantitative confocal microscopy, Western blot, flow cytometry and histochemistry. Cultured macrophages were stimulated with 10% cigarette smoke extract (CSE), with or without presence of non-antibiotic macrolides 2'-desoxy-9-(S)-erythromycylamine and azithromycin-based 2'-desoxy molecule. Cigarette smoke and CSE induced in macrophages significant (p<0.05) upregulation of cleaved IL-1β, which was associated with increased NLRP3. Macrophage senescence was shown by increased lipofuscin and p53 but decreased perinuclear lamin B1. Significantly decreased surface CD9 and CD81 were detected in COPD patients’ alveolar macrophages, and in CSE-treated MDM, compared to controls. Co-treatment of CSE-stimulated MDM with azithromycin or non-antibiotic macrolides recovered CD9/CD81 and lamin B1 expression and inhibited NLRP3-associated cleavage of IL-1β. We conclude that alveolar macrophages in COPD and/or response to cigarette smoke undergo NLRP3 inflammasome activation and accelerated senescence; both processes can potentially be targeted by nonantibiotic macrolides.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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