The Network Of Foxp3, RORγt And IL-17in Irradiation-induced Lung Injury And The Modulation By Endostar

1. ObjectiveTo observe the expression of Foxp3,RORγt and IL-17in the murine model ofirradiation-induced lung injury. To illuminate the underlying mechanisms. To studythe modulation of Endostar on the effects of the expressions of these factors in themice after single12Gy thoracic irradiation, and explore a possible effective way toprevent or treat irradiation induced lung injury.2. Methods1. To establish the murine model of irradiation-induced lung injury and to detect theexpression of Foxp3, RORγt IL-17and IL-17F. Mice were randomly divided into2groups: those that received normal sodium but not irradiation(NT group), those thatunderwent irradiation and normal sodium(RT group). Three random mice in everygroup were sacrificed at the time points. The left lungs were for HE staining, Massonstaining and immunohistochemistry of TGF-β1and TNF-α. The right ones were forwestern-blot and RT-PCR analysis of Foxp3, RORγt, IL-17, IL-17F, TGF-β1and TNF-α.2. To investigate the modulation of Foxp3, RORγt and IL-17expressionby Endostar. mice were randomly divided into4groups: those that received normalsodium but not irradiation(NT group), those that underwent irradiation and normalsodium(RT group),those that received both Endostar and irradiation(RT+EN group),those that received Endostar but not irradiation(EN group). The left lungs were forHE staining, Masson staining and immunohistochemistry of TGF-β1and TNF-α, andthe left ones were for western-blot and RT-PCR.3. ResultsIn Multiple time points, HE staining showed II～III degree of alveolitis in the RTgroup but no obvious alveolitis in the NT group. Collagen deposition in the RT groupwas much more than that in the NT group. The Foxp3and RORγt mRNA content of theRT group were significantly higher than the NT one in Multiple time points. Statisticalcomparison of the TGF-β1，RORγt and IL17f expressions revealed significantdifference between the RT group and the NT group at week4and8post-irradiation.Significant increases in TGF-β1and TNF-α expression were observed in Multiple timepoints for the RT groups compared to the NT groups.The degree of alveolitis observed in the RT+EN group was lower than theRT group by HE staining. Collagen deposition in the RT group was much more thanthat in the RT+EN group. The Foxp3RORγt、TGF-β1and TNF-α mRNA content ofthe RT+EN group were significantly lower than the RT one in Multiple time points.Significant increases in RORγt and TGF-β1expression were observed at week4post-irradiation for the RT groups compared to the NT groups. Statistical comparisonof the Foxp3，RORγt，TGF-β1and TNF-α expressions revealed significant differencebetween the RT group and RT+EN group at week8post-irradiation. 4. ConclusionThis study demonstrates a significant increase of Foxp3、RORγt、TGF-β1andTNF-α(on mRNA and protein level) in the lung tissue of the murine model of irradi-ationinduced lung injury. Foxp3and RORγt were the new insights into irradiation-induced lung injury and may provide new mechanism of irradiation-induced lunginjury. Endostar could degrade the levels of irradiation-induced Foxp3、RORγt、TGF-β1and TNF-α.