연세의대, 서울대 / 김현중, 조재호*, 김진모*
Abstract
Radiation therapy is an important modality in the treatment of lung cancer, but it can lead to radiation pneumonitis, and eventually radiation fibrosis. To date, only few available drugs can effectively manage radiation-induced pulmonary fibrosis. Lipoxins are endogenous molecules exhibit anti-inflammatory and pro-resolving effects. These molecules play a vital role in reducing excessive tissue injury and chronic inflammation; however, their effects on radiation-induced lung injury (RILI) are unknown. In this study, we investigated the effects of lipoxin A4 (LXA4) on RILI using our specialized small-animal model of RILI following focal-ablative lung irradiation (IR). LXA4 significantly inhibited immune-cell recruitment and reduced IR-induced expression of pro-inflammatory cytokines and fibrotic proteins in the lung lesion sites. In addition, micro-CT revealed that LXA4 reduced IR-induced increases in lung consolidation volume. The flexiVentTM assays showed that LXA4 significantly reversed IR-induced lung function damage. Moreover, LXA4 downregulated the activities of NF-κB and the Smad-binding element promoters. The expression of FPR2, an LXA4 receptor, increased during the development of IR-induced pulmonary fibrosis, whereas silencing of endogenous LXA4 using an antagonist (WRW4) or FPR2 siRNA resulted in impaired development of pulmonary fibrosis in response to IR. Collectively, these data suggest that LXA4 could serve as a potent therapeutic agent for alleviating RILI.
Affiliations
Hyunjung Kim 1 , Sung-Hyo Park 1 , Song Yee Han 1 , Yun-Sil Lee 2 , Jaeho Cho 3 , Jin-Mo Kim 4 5
1 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
2 Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea.
3 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea. jjhmd@yuhs.ac.
4 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea. jmk0831@snu.ac.kr.
5 Department of Manufacturing Pharmacy, Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, South Korea. jmk0831@snu.ac.kr.
편집위원
방사선치료는 효과적인 폐암 치료법이지만, 폐섬유증을 유발할 수 있으며, 현재까지 그 치료법은 매우 제한적이다. 본 연구는 specialized animal model을 통해 anti-inflammatory effect를 갖는 lipoxin A4(LXA4)가 radiation-induced lung injury (RILI)에 대한 치료제가 될 수 있음을 제시하였다.
2020-10-05 17:46:12
편집위원2
방사선에 의해 유도되는 폐섬유화에서 LXA 4-FPR2 signaling과 TGF-β/Smad signaling 의 crosstalk을 규명함으로써 방사선에 의한 폐섬유화 기전에 대한 다양한 방향을 제시한 연구라 생각됨.
2020-10-05 17:46:56