Caffeine Inhibits NLRP3 Inflammasome Activation by Suppressing MAPK/NF-κB and A2aR Signaling in LPS-Induced THP-1 Macrophages

International Journal of Biological Sciences
Weiming ZhaoXiaohui Gong

Abstract

Excessive inflammation induced by various risk factors is associated with the development of bronchopulmonary dysplasia (BPD). Caffeine exerts potent anti-inflammatory effects as a clinical preventive medicine for BPD. Recently, NLRP3 inflammasome activation has been demonstrated to be essential for the pathogenesis of BPD. In the present study, we aimed to investigate the effects of caffeine on NLRP3 inflammasome activation in LPS-induced THP-1 macrophages and to explore the underlying the detailed mechanism. We found that caffeine significantly reduced NLRP3 expression, ASC speck formation, and caspase 1 cleavage and therefore decreased IL-1β and IL-18 secretion in THP-1 macrophages. Caffeine also markedly decreased the phosphorylation levels of MAPK and NF-κB pathway members, further suppressing the translocation of NF-κB in THP-1 macrophages. Moreover, silencing of the caffeine-antagonized adenosine A2a receptor (A2aR) significantly decreased cleaved caspase 1 expression in THP-1 macrophages by reducing ROS production. Given these findings, we conclude that caffeine inhibits NLRP3 inflammasome activation by suppressing MAPK/NF-κB signaling and A2aR-associated ROS production in LPS-induced THP-1 macrophages.

Citations

Oct 10, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ettore LignelliRory E Morty
Aug 20, 2020·Journal of Cellular and Molecular Medicine·Jia-He ChenGuo-Ping Zhou
Dec 10, 2020·Médecine sciences : M/S·Damien Veret, Jean-Marc Brondello
May 9, 2021·Nature Immunology·Min ZhengThirumala-Devi Kanneganti
May 20, 2021·Inflammation·Ming-Ye ChenDong-Yun Ouyang
Jun 3, 2021·International Journal of Molecular Sciences·Bianca S Romero-MartínezEdgar Flores-Soto

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Methods Mentioned

BETA
PMA
flow cytometry
ELISA
PCR
transfection
Assay

Software Mentioned

Graph Pad Prism

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