MCC950 ameliorates radiation induced lung injury through modulating macrophage polarization

To investigate the beneficial effect of NLRP3 inflammasome specific inhibitor MCC950 on radiation induced lung injury (RILI) and its potential mechanism in mice. A total of 36 female C57BL/6J mice aged 7 weeks were randomly assigned to the control group, the irradiation group, and the irradiation plus MCC950 group. The irradiation group and irradiation plus MCC950 group mice were exposed to whole-thorax radiation at a single 20 Gy dose. The control group mice were provided with an irradiation dose of 0 Gy. The irradiation plus MCC950 group mice were treated with MCC950 following irradiation. The mice in control group and irradiation group were treated with the same amount of normal saline. After 12 weeks, the body weight and the dry and wet lung weight of the three groups mice were measured to assess the lung coefficient (the ratio of the lung wet weigh to the body weight of each mouse) and the wet-to-dry lung weight ratio (weight of the wet lung/weight of the dry lung). The degree of lung tissue injury was assessed using hematoxylin eosin staining. Western blotting was performed to evaluate the expression of macrophage polarization markers, NLRP3 inflammasome, and inflammatory factors. The experimental results indicated that compared with the control group mice, the lung coefficient, wet-to-dry lung weight ratio, the lung tissue injury score, and the protein expression of M1 macrophage markers (CD86), NLRP3 inflammasome (NLRP3, ASC, and Caspase-1), and inflammatory cytokines (Pro-IL-1β, IL-1β, IL-18, and TNF-a) of the irradiation group mice were dramatically enhanced, whereas the protein expression of M2 macrophage markers (CD163) was significantly decreased. Compared with the irradiation group mice, irradiation plus MCC950 group mice had higher protein expression of CD163, and remarkably reduced the lung coefficient, wet-to-dry lung weight ratio, the lung tissue injury score, and the protein expression of CD86, NLRP3, ASC, Caspase-1, Pro-IL-1β, IL-1β, IL-18, and TNF-‍a. The above results demonstrated that MCC950 ameliorates RILI through modulating macrophage polarization, and it promises to be an intervention agent against RILI.