ResolvinD1 reduces apoptosis and inflammation in primary human alveolar epithelial type 2 cells

Xie, Wanli; Wang, Huiqing; Liu, Qing; Li, Yongsheng; Wang, Jianjun; Yao, Shanglong; Wu, Qingping

doi:10.1038/labinvest.2016.31

Cited by 14 publications

(8 citation statements)

References 47 publications

(64 reference statements)

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“…Inappropriate or massive stimulation of autophagy can actually facilitate cell death. Our previous work showed that apoptotic pulmonary cells also plays a critical role during the process of ALI [44]. In addition, MV or CS-induced autophagy and apoptosis in fetal rat lung epithelial cells [45], suggesting that such autophagic cell death exhibits an essential role in MV or CS model.…”

Section: Discussionmentioning

confidence: 95%

JAK2/STAT1-mediated HMGB1 translocation increases inflammation and cell death in a ventilator-induced lung injury model

Liu

Xie

Wang

et al. 2019

Laboratory Investigation

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Janus kinase 2/signal transducer and activators of transcription 1 (JAK2/STAT1) signaling is a common pathway that contributes to numerous inflammatory disorders, including different forms of acute lung injury (ALI). However, the role of JAK2/STAT1 in ventilator-induced lung injury (VILI) and its underlying mechanism remain unclear. In this study, using lipopolysaccharide (LPS) inhalation plus mechanical ventilation as VILI mouse model, we found that the administration of JAK2 inhibitor AZD1480 markedly attenuated lung destruction, diminished protein leakage, and inhibited cytokine release. In addition, when mouse macrophage-like RAW 264.7 cells were exposed to LPS and cyclic stretch (CS), AZD1480 prevented cell autophagy, reduced apoptosis, and suppressed lactate dehydrogenase release by downregulating JAK2/STAT1 phosphorylation levels and inducing HMGB1 translocation from the nucleus to the cytoplasm. Furthermore, HMGB1 and STAT1 knockdown attenuated LPS+CS-induced autophagy and apoptosis in RAW 264.7 cells. In conclusion, these findings reveal the connection between the JAK2/STAT1 pathway and HMGB1 translocation in mediating lung inflammation and cell death in VILI, suggesting that these molecules may serve as novel therapeutic targets for VILI.

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Section: Discussionmentioning

confidence: 95%

JAK2/STAT1-mediated HMGB1 translocation increases inflammation and cell death in a ventilator-induced lung injury model

Liu

Xie

Wang

et al. 2019

Laboratory Investigation

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“…Proresolving lipid mediators, including lipoxins, resolvins, protectins, and maresins, are syn-thesized from omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) and omega-6 fatty acids (arachidonic acid) (5,24). RvD1 is a kind of resolvin that displays dramatic inflammation-proresolving activities (35,36). FPR2/ALX is a G protein-coupled receptor with multiple binding partners, including the endogenous lipid mediators RvD1, lipoxin A4, and the Ca 2ϩ -dependent phospholipid-binding protein annexin A1.…”

Section: Discussionmentioning

confidence: 99%

Resolvin D1 attenuates mechanical stretch-induced pulmonary fibrosis via epithelial-mesenchymal transition

Yang

Xia

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical ventilation-induced pulmonary fibrosis plays an important role in the high mortality rate of acute respiratory distress syndrome (ARDS). Resolvin D1 (RvD1) displays potent proresolving activities. Epithelial-mesenchymal transition (EMT) has been proved to be an important pathological feature of lung fibrosis. This study aimed to investigate whether RvD1 can attenuate mechanical ventilation-induced lung fibrosis. Human lung epithelial (BEAS-2B) cells were pretreated with RvD1 for 30 min and exposed to acid for 10 min before being subjected to mechanical stretch for 48 h. C57BL/6 mice were subjected to intratracheal acid aspiration followed by mechanical ventilation 24 h later (peak inspiratory pressure 22 cmH2O, positive end-expiratory pressure 2 cmH2O, and respiratory rate 120 breaths/min for 2 h). RvD1 was injected into mice for 5 consecutive days after mechanical ventilation. Treatment with RvD1 significantly inhibited mechanical stretch-induced mesenchymal markers (vimentin and α-smooth muscle actin) and stimulated epithelial markers (E-cadherin). Tert-butyloxycarbonyl 2 (BOC-2), a lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) antagonist, is known to inhibit ALX/FPR2 function. BOC-2 could reverse the beneficial effects of RvD1. The antifibrotic effect of RvD1 was associated with the suppression of Smad2/3 phosphorylation. This study demonstrated that mechanical stretch could induce EMT and pulmonary fibrosis and that treatment with RvD1 could attenuate mechanical ventilation-induced lung fibrosis, thus highlighting RvD1 as an effective therapeutic agent against pulmonary fibrosis associated with mechanical ventilation.

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“…However, LXA4 restored the function of the epithelial barriers by reversing the inhibition of LPS on AT II cell proliferation and reducing apoptosis of AT II cells induced by LPS. In addition, LXA4 promoted primary AT II cell proliferation and reduced apoptosis induced by LPS [25, 26].…”

Section: Discussionmentioning

confidence: 99%

Lipoxin A4 ameliorates lipopolysaccharide-induced lung injury through stimulating epithelial proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition

Yang

Chen

et al. 2019

Respir Res

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Background Acute respiratory distress syndrome (ARDS) is characterized by alveolar epithelial disruption. Lipoxins (LXs), as so-called “braking signals” of inflammation, are the first mediators identified to have dual anti-inflammatory and inflammatory pro-resolving properties. Methods In vivo, lipoxinA 4 was administrated intraperitoneally with 1 μg/per mouse after intra-tracheal LPS administration (10 mg/kg). Apoptosis, proliferation and epithelial–mesenchymal transition of AT II cells were measured by immunofluorescence. In vitro, primary human alveolar type II cells were used to model the effects of lipoxin A 4 upon proliferation, apoptosis and epithelial–mesenchymal transition. Results In vivo, lipoxin A 4 markedly promoted alveolar epithelial type II cells (AT II cells) proliferation, inhibited AT II cells apoptosis, reduced cleaved caspase-3 expression and epithelial–mesenchymal transition, with the outcome of attenuated LPS-induced lung injury. In vitro, lipoxin A 4 increased primary human alveolar epithelial type II cells (AT II cells) proliferation and reduced LPS induced AT II cells apoptosis. LipoxinA 4 also inhibited epithelial mesenchymal transition in response to TGF-β 1 , which was lipoxin receptor dependent. In addition, Smad3 inhibitor (Sis3) and PI3K inhibitor (LY294002) treatment abolished the inhibitory effects of lipoxinA 4 on the epithelial mesenchymal transition of primary human AT II cells. Lipoxin A 4 significantly downregulated the expressions of p-AKT and p-Smad stimulated by TGF-β 1 in primary human AT II cells. Conclusion LipoxinA 4 attenuates lung injury via stimulating epithelial cell proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition. Electronic supplementary material The online version of this article (10.1186/s12931-019-1158-z) contains supplementary material, which is available to authorized users.

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ResolvinD1 reduces apoptosis and inflammation in primary human alveolar epithelial type 2 cells

Cited by 14 publications

References 47 publications

JAK2/STAT1-mediated HMGB1 translocation increases inflammation and cell death in a ventilator-induced lung injury model

JAK2/STAT1-mediated HMGB1 translocation increases inflammation and cell death in a ventilator-induced lung injury model

Resolvin D1 attenuates mechanical stretch-induced pulmonary fibrosis via epithelial-mesenchymal transition

Lipoxin A4 ameliorates lipopolysaccharide-induced lung injury through stimulating epithelial proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition

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