Exogenous 8-Hydroxydeoxyguanosine Attenuates PM<sub>2.5</sub>-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation
Particulate matter 2.5 (PM<sub>2.5</sub>) 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 inflamma...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/6/1189 |
| _version_ | 1827738817739620352 |
|---|---|
| author | Jihye Bang Kuk Hui Son Hye-Ryeon Heo Eunsook Park Hyun-Jeong Kwak Kyung-Ok Uhm Myung-Hee Chung Young-Youl Kim Hyun Joung Lim |
| author_facet | Jihye Bang Kuk Hui Son Hye-Ryeon Heo Eunsook Park Hyun-Jeong Kwak Kyung-Ok Uhm Myung-Hee Chung Young-Youl Kim Hyun Joung Lim |
| author_sort | Jihye Bang |
| collection | DOAJ |
| description | Particulate matter 2.5 (PM<sub>2.5</sub>) 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</sub>-induced lung injury, we evaluated whether 8-OHdG decreased PM<sub>2.5</sub>-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</sub> 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</sub>-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</sub>. |
| first_indexed | 2024-03-11T02:49:24Z |
| format | Article |
| id | doaj.art-2114eb8a15fe464fb4aad3506ff6cb17 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T02:49:24Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-2114eb8a15fe464fb4aad3506ff6cb172023-11-18T09:02:42ZengMDPI AGAntioxidants2076-39212023-05-01126118910.3390/antiox12061189Exogenous 8-Hydroxydeoxyguanosine Attenuates PM<sub>2.5</sub>-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome ActivationJihye Bang0Kuk Hui Son1Hye-Ryeon Heo2Eunsook Park3Hyun-Jeong Kwak4Kyung-Ok Uhm5Myung-Hee Chung6Young-Youl Kim7Hyun Joung Lim8Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, National Institute of Health, Osong Health Technology Administration Complex 187, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Republic of KoreaGachon University Gil Medical Center, Department of Thoracic and Cardiovascular Surgery, College of Medicine, Gachon University, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon 21565, Republic of KoreaDivision of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, National Institute of Health, Osong Health Technology Administration Complex 187, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Republic of KoreaDivision of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, National Institute of Health, Osong Health Technology Administration Complex 187, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Republic of KoreaMajor of Life Science, Division of Bioconvergence, College of Convergence and Integrated Science, Kyonggi University, 154-42 Gwanggosan-ro, Yeongtong-gu, Suwon-si 16227, Republic of KoreaDivision of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, National Institute of Health, Osong Health Technology Administration Complex 187, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Republic of KoreaLee Gil Ya Cancer and Diabetes Institute, Gachon University, 155, Gaetbeol-ro, Yeonsu-ku, Incheon 21999, Republic of KoreaDivision of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, National Institute of Health, Osong Health Technology Administration Complex 187, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Republic of KoreaDivision of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, National Institute of Health, Osong Health Technology Administration Complex 187, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Republic of KoreaParticulate matter 2.5 (PM<sub>2.5</sub>) 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</sub>-induced lung injury, we evaluated whether 8-OHdG decreased PM<sub>2.5</sub>-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</sub> 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</sub>-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</sub>.https://www.mdpi.com/2076-3921/12/6/1189particulate matter 2.5lung injuryreactive oxygen species8-hydroxydeoxyguanosineNLRP3 inflammasome |
| spellingShingle | Jihye Bang Kuk Hui Son Hye-Ryeon Heo Eunsook Park Hyun-Jeong Kwak Kyung-Ok Uhm Myung-Hee Chung Young-Youl Kim Hyun Joung Lim Exogenous 8-Hydroxydeoxyguanosine Attenuates PM<sub>2.5</sub>-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation Antioxidants particulate matter 2.5 lung injury reactive oxygen species 8-hydroxydeoxyguanosine NLRP3 inflammasome |
| title | Exogenous 8-Hydroxydeoxyguanosine Attenuates PM<sub>2.5</sub>-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation |
| title_full | Exogenous 8-Hydroxydeoxyguanosine Attenuates PM<sub>2.5</sub>-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation |
| title_fullStr | Exogenous 8-Hydroxydeoxyguanosine Attenuates PM<sub>2.5</sub>-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation |
| title_full_unstemmed | Exogenous 8-Hydroxydeoxyguanosine Attenuates PM<sub>2.5</sub>-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation |
| title_short | Exogenous 8-Hydroxydeoxyguanosine Attenuates PM<sub>2.5</sub>-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation |
| title_sort | exogenous 8 hydroxydeoxyguanosine attenuates pm sub 2 5 sub induced inflammation in human bronchial epithelial cells by decreasing nlrp3 inflammasome activation |
| topic | particulate matter 2.5 lung injury reactive oxygen species 8-hydroxydeoxyguanosine NLRP3 inflammasome |
| url | https://www.mdpi.com/2076-3921/12/6/1189 |
| work_keys_str_mv | AT jihyebang exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation AT kukhuison exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation AT hyeryeonheo exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation AT eunsookpark exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation AT hyunjeongkwak exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation AT kyungokuhm exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation AT myungheechung exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation AT youngyoulkim exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation AT hyunjounglim exogenous8hydroxydeoxyguanosineattenuatespmsub25subinducedinflammationinhumanbronchialepithelialcellsbydecreasingnlrp3inflammasomeactivation |