Parthenolide ameliorates LPS-induced acute lung injury by the miR-141-3p/PDCD4 axis
This study aims to explore the effects and regulatory mechanism of parthenolide(PTL)on LPS-induced acute lung injury(ALI).C57BL/6 mice were used to establish the ALI model by a single intratracheal administration of LPS(4 mg/kg).For in vitro LPS-induced cell injury,MLE-12 cells were treated with 1 μg/mL LPS.Mice were randomly divided into four groups:control group,LPS group,LPS+5 mg/kg PTL doses group,and LPS+10 mg/kg PTL doses group,with 10 mice in each group.H-E staining was used to examine the pathological changes of lung tissue.Lung tissues were collected and the ratio of wet weight(W)to dry weight(D)was measured.IL-1β,IL-6,and TNF-α content in alveolar lavage fluid and cells was measured by ELISA.The levels of miR-141-3p and programmed cell death 4(PDCD4)were measured by qRT-PCR and Western blotting,respectively.Cell viability and apoptosis were determined by CCK-8 method and FACS,respectively.The results showed that compared to those of the control group,the lung tissue W/D ratio,TNF-α,IL-1β,IL-6,and PDCD4 expression levels were significantly increased(P＜0.05).Alveolar wall thickening,diffuse pulmonary interstitial hemorrhage,and inflam-matory infiltration were increased and the pathological score of lung tissue was also increased(P＜0.05),while the expression of miR-141-3p was decreased in the LPS group(P＜0.05).Compared to those of the LPS group,the W/D ratio,TNF-α,IL-1β,IL-6,and PDCD4 levels were decreased(P＜0.05),alveolar wall thickening was alleviated,diffuse pulmonary interstitial hemorrhage and inflammatory infiltration were reduced,pathological scores of lung tissue were decreased(P＜0.05),and the expression of miR-141-3p was increased in LPS+5 mg/kg PTL doses group and LPS+10 mg/kg PTL doses group(P＜0.05)in a dose-dependent manner.Compared to those of the control group,the cell viability and miR-141-3p expression were decreased(P＜0.05),while the apoptosis rate and the levels of TNF-α,IL-1β,IL-6,and PDCD4 were increased in the LPS group(P＜0.05).The cell viability and miR-141-3p expression were increased(P＜0.05),while the apoptosis rate and the levels of TNF-α,IL-1β,IL-6,and PDCD4 were decreased after 5 or 10 μmol/L doses of PTL treatment(P＜0.05)in a dose-dependent manner.Furthermore,PDCD4 was shown to target miR-141-3p.The study suggests that PTL inhibits inflammation to alleviate LPS-induced ALI by upregulating the miR-141-3p/PDCD4 axis.
acute lung injuryparthenolidemicroRNA-141-3pprogrammed cell death 4
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