연세의대 / 김상연, 조재호*
Lung inflammation and fibrosis are common side effects of radiotherapy that can lead to serious reduction in the quality of life of patients. However, no effective treatment is available, and the mechanisms underlying its pathophysiology are poorly understood. Irradiation increases formyl peptide receptor 2 (FPR2) expression in lung tissue, and FPR2 agonists are known to promote the uptake of apoptosis cells, referred to as efferocytosis that is a hallmark of the resolution of inflammation. Herein, in a mouse model of radiation-induced lung injury (RILI), efferocytosis was induced by injecting apoptotic cells into the lung through the trachea, and its correlation with FPR expression and the effect of efferocytosis and FPR expression on RILI were assessed. Interestingly, when apoptotic cells were injected into the lung, the radiation-induced increase in FPR2 expression was further amplified. In the mouse model of RILI, apoptotic cell instillation reduced the volume of the damaged lung and prevented the decrease in lung function. Additionally, the expression of inflammatory cytokines, fibrosis-related markers, and oxidative stress-related markers was reduced by apoptotic cell instillation. Co-administration of apoptotic Jurkat cells and WRW4, the FPR2 antagonist, reversed these effects. These findings suggest that efferocytosis induced by apoptotic cell instillation and enhanced FPR2 expression attenuate RILI, thereby alleviating lung inflammation and fibrosis.
Sang Yeon Kim 1 , Jin-Mo Kim 2 , Son Ro Lee 1 , Hyun-Jin Kim 1 , Jae Hee Lee 1 , Ho Lim Choi 1 , Yoon-Jin Lee 3 , Yun-Sil Lee 4 , Jaeho Cho 5
1 Department of Radiation Oncology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
2 Department of Radiation Oncology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea; Department of Manufacturing Pharmacy, Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, South Korea.
3 Korea Institute of Radiological and Medical Science, Seoul, South Korea.
4 Graduate School of Pharmaceutical Science, Ewha Womans University, Seoul, South Korea.
5 Department of Radiation Oncology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. Electronic address: email@example.com.