Exogenous 8-Hydroxydeoxyguanosine Attenuates PM[sub.2.5]-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation

• Published in: Antioxidants Vol. 12; no. 6
• Main Authors: Bang, Jihye, Son, Kuk Hui, Heo, Hye-Ryeon, Park, Eunsook, Kwak, Hyun-Jeong, Uhm, Kyung-Ok, Chung, Myung-Hee, Kim, Young-Youl, Lim, Hyun Joung
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.05.2023
• Subjects: B cells; Inflammation; Interleukins; Polycyclic aromatic hydrocarbons; Statistics; Tumor necrosis factor; South Korea
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox12061189

Particulate matter 2.5 (PM[sub.2.5]) induces lung injury by increasing the generation of reactive oxygen species (ROS) and inflammation. ROS aggravates NLRP3 inflammasome activation, which activates caspase-1, IL-1β, and IL-18 and induces pyroptosis; these factors propagate inflammation. In contrast, treatment with exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases RAC1 activity and eventually decreases dinucleotide phosphate oxidase (NOX) and ROS generation. To establish modalities that would mitigate PM[sub.2.5]-induced lung injury, we evaluated whether 8-OHdG decreased PM[sub.2.5]-induced ROS generation and NLRP3 inflammasome activation in BEAS-2B cells. CCK-8 and lactate dehydrogenase assays were used to determine the treatment concentration. Fluorescence intensity, Western blotting, enzyme-linked immunosorbent assay, and immunoblotting assays were also performed. Treatment with 80 μg/mL PM[sub.2.5] increased ROS generation, RAC1 activity, NOX1 expression, NLRP3 inflammasome (NLRP3, ASC, and caspase-1) activity, and IL-1β and IL-18 levels in cells; treatment with 10 μg/mL 8-OHdG significantly attenuated these effects. Furthermore, similar results, such as reduced expression of NOX1, NLRP3, ASC, and caspase-1, were observed in PM[sub.2.5]-treated BEAS-2B cells when treated with an RAC1 inhibitor. These results show that 8-OHdG mitigates ROS generation and NLRP3 inflammation by inhibiting RAC1 activity and NOX1 expression in respiratory cells exposed to PM[sub.2.5].