{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:21:49Z","timestamp":1792804909574,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2022R1A2C3011611"],"award-info":[{"award-number":["NRF-2022R1A2C3011611"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Women in Science, Engineering, and Technology (WISET) Returners into R&D Program","award":["WISET Gyeongbok 2023-Da-27"],"award-info":[{"award-number":["WISET Gyeongbok 2023-Da-27"]}]},{"name":"Women in Science, Engineering, and Technology (WISET) Returners into R&D Program","award":["WISET Gyeongbok 2023-Da-28"],"award-info":[{"award-number":["WISET Gyeongbok 2023-Da-28"]}]},{"name":"Ministry of Science and ICT (MSIT), and faculty research grants from Yonsei University College of Medicine","award":["6-2024-0170"],"award-info":[{"award-number":["6-2024-0170"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science and ICT (MSIT), and faculty research grants from Yonsei University College of Medicine","award":["6-2024-0195"],"award-info":[{"award-number":["6-2024-0195"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiation-induced lung inflammation (RILI) is a major complication of thoracic radiotherapy, characterized by excessive inflammation and subsequent fibrosis that compromise pulmonary function and treatment outcomes. This study explores the pharmacological properties of a newly synthesized Lipoxin A4 analogue (CYNC-2) to mitigate RILI by modulating the AMP-activated protein kinase (AMPK)\/NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome pathway. A murine RILI model was established in mice by delivering a single high-dose (ablative) X-ray irradiation to the left lung. Mice in the treatment group received CYNC-2 via tail-vein injection three times per week for 2 weeks. The effects of CYNC-2 on RILI were evaluated histological, immunohistochemical analysis of lung tissues, cytokine profiling, lung function testing using a FlexiVent system, and micro-computed tomography (micro-CT) imaging of lung damage. In parallel, two human lung cell lines\u2014L132 (normal bronchial epithelial cells) and A549 (lung carcinoma cells)\u2014were irradiated with 6 Gy X-rays and treated with CYNC-2 to assess cell viability and changes in AMPK\/NLRP3 pathway markers via qPCR and immunofluorescence. Lung tissue sample from patients who underwent thoracic radiotherapy were also examined to validate key findings. CYNC-2 activated AMPK and inhibited mTOR signaling, which suppressed NLRP3 inflammasome activation and led to reduced secretion of pro-inflammatory cytokines (IL-1\u03b2, IL-6, and TGF-\u03b21). In vitro, CYNC-2 mitigated radiation-induced inflammatory responses and preserved cellular viability. Overall, CYNC-2 effectively dampened acute pulmonary in the RILI model. These findings suggest that targeting the AMPK\/NLRP3 inflammasome pathway via a stable LXA4 analogue such as CYNC-2 is a promising therapeutic strategy to improve clinical outcomes for patients receiving thoracic radiation therapy.<\/jats:p>","DOI":"10.3390\/ijms262210832","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:57:55Z","timestamp":1762765075000},"page":"10832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modulation of AMPK\/NLRP3 Signaling Mitigates Radiation-Induced Lung Inflammation by a Synthetic Lipoxin A4 Analogue"],"prefix":"10.3390","volume":"26","author":[{"given":"Sun Ho","family":"Min","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Ho","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, CHA University, Pocheon-si 11160, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunjoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5476-7631","authenticated-orcid":false,"given":"Ronglan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn Ji","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Hyun","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, CHA University, Pocheon-si 11160, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9486-4122","authenticated-orcid":false,"given":"Sang Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Department of Food and Nutrition, College of Health Science, Honam University, Gwangju 62399, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7281-1205","authenticated-orcid":false,"given":"Younghwa","family":"Na","sequence":"additional","affiliation":[{"name":"College of Pharmacy, CHA University, Pocheon-si 11160, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9966-5157","authenticated-orcid":false,"given":"Jaeho","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ccm.2016.12.004","article-title":"Radiation Pneumonitis","volume":"38","author":"Bledsoe","year":"2017","journal-title":"Clin. 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