Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis

Abstract

Melatonin is a well-known anti-inflammatory and antioxidant molecule, which plays a crucial role in various physiological functions. In this study, mice received a single dose of 15 Gy radiation delivered to the lungs and daily intraperitoneal administration of melatonin. After 7 days, mice were processed to harvest either bronchoalveolar lavage fluid for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that melatonin markedly alleviated the oxidative stress and injury, especially suppressing the infiltration of macrophages (CD11b+CD11c−) and neutrophils (CD11b+Ly6G+) to the irradiated lungs. Moreover, in the irradiated RAW 264.7 cells, melatonin blocked the NLRP3 inflammasome activation accompanied with the inhibition of the IL-1β release and caspase-1 activity. However, melatonin restored the downregulated miR-30e levels. Quantitative PCR analysis of miR-30e and NLRP3 indicated the negative correlation between them. Notably, immunofluorescence staining showed that overexpression of miR-30e dramatically diminished the increased NLRP3 expression. Luciferase reporter assay confirmed that NLRP3 was a target gene of miR-30e. Western blotting revealed that transfection with miR-30e mimics markedly reduced the expressions of NLRP3 and cleaved caspase-1, whereas this phenomenon was reversed by the miR-30e inhibitor. Consistent with this, the beneficial effect of melatonin under irradiated exposure was blunted in cells transfected with anti-miR-30e. Collectively, our results demonstrate that the NLRP3 inflammasome contributed to the pathogenesis of radiation-induced lung injury. Meanwhile, melatonin exerted its protective effect through negatively regulating the NLRP3 inflammasome in macrophages. The melatonin-mediated miR-30e/NLRP3 signaling may provide novel therapeutic targets for radiation-induced injury.

Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production

“…Generally, the prooxidant effects of melatonin have been reported in vitro cell culture systems and dependent on concentration, cell type, and the duration of the treatment [22]. The antioxidant capacity of melatonin has been well established both in vitro and in vivo, while its prooxidant property has been observed at the same time [14,[22][23][24][25]. The relevance of this finding is unclear, therefore, more studies addressing this issue are necessary.…”

Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed

“…Knowing the anti-inflammatory capacity of melatonin, we urge the rational use of this substance for ALI/ARDS-mediated symptoms. Indeed, the melatonin-controlled regulation of NLRP3 was shown in radiation-induced lung injury or respiratory disturbances, where melatonin distinctly reduced the infiltration of macrophages and neutrophils into the lung by inhibition of the NLRP3 inflammasome [26,[57][58][59].…”

In-line treatments and clinical initiatives to fight against COVID-19 outbreak

“…Melatonin is a bioactive agent with a lot of health-promoting properties. It is also found effective in radiation, bacteria or virus-induced acute respiratory syndrome [ 166 ]. Based on the evidence, it is supposed to show some positive effects in the treatment of COVID-19 induced acute lung injury, acute respiratory distress syndrome, and pneumonia.…”