MiR-223 protects mice from acute radiation-induced lung injury by inhibiting NLRP3

Abstract

Objective To investigate the radioprotective function and its mechanism of miR-223 in acute radiation-induced lung injury in mice. Methods Forty female C57BL/6 J mice were randomly divided into healthy control group, irradiation group, irradiation plus miR-223 group and irradiation plus NC group. Radiation groups were exposed with a single dose of 15 Gy of 6 MV X-rays delivered by a linear accelerator. The mice in drug group were administered by tail vein injection with miR-223 agomir or agomir-NC every other day from 1 d before irradiation to 14 d after irradiation. The lung tissue samples of mice were taken at 14 d post-irradiation. The pathological changes were observed by HE staining. The localization and expressions of IL-1β and IL-18 were observed by immunohistochemistry (IHC). Real-time PCR was used to detect miR-223, but NLRP3 mRNA expression in lung tissue. Western blot was used to detect the protein expressions of NLRP3 and Caspase-1, and ELISA assay was used to detect the expressions of IL-1β and IL-18 in lung homogenate. Results Radiation decreased the expression of miR-223, but increased the expression of NLRP3 in lung tissue. Administration of miR-223 agomir inhibited the expression of NLRP3 and attenuated lung inflammation. HE and IHC staining showed that miR-223 reduced the acute inflammatory response and the expressions of IL-1β and IL-18 in lung tissue compared with irradiation group (t=10.16, 6.00, P<0.05). The expressions of NLRP3 and Caspase-1 protein in lung tissue of irradiated plus miR-223 group was lower than that in the irradiation alone group (t=12.47, 4.95, P<0.05). ELISA assay also showed a decrease of inflammatory factors IL-1β and IL-18 in lung tissue homogenate of the irradiation plus miR-223 group (t=8.22, 8.47, P<0.05). Conclusions MiR-223 effectively reduces the secretion of radiation-induced inflammatory factors IL-1β and IL-18 by inhibiting the expression of NLRP3 in lung tissue of mice, and thus has protective effect on radiation-induced lung injury. Key words: miR-223; Radiation-induced lung injury; NLRP3