Overexpression of CXCL14 Alleviates Ventilator-Induced Lung Injury Through the Downregulation of PKM2-Mediated Cytokine Production

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2020 Aug 11

PMID 32774150

Citations 3

Authors

Rui Zhu

Yan-Qing Lei

Dong-Chi Zhao

Affiliations

Soon will be listed here.

Abstract

Ventilator-induced lung injury (VILI) is one of the most common complications of mechanical ventilation (MV), which strongly impacts the outcome of ventilated patients. Current evidences indicated that inflammation is a major contributor to the pathogenesis of VILI. Our results showed that MV induced excessive proinflammatory cytokine productions together with decreased CXCL14 and increased PKM2 expressions in injured lungs. In addition, CXCL14 overexpression downregulated PKM2 expression and attenuated VILI with reduced inflammation. Moreover, the overexpression of PKM2 markedly diminished the protective effects of CXCL14 against VILI as reflected by worsened morphology and increased cytokine production, whereas PKM2 knockdown decreased cytokine production and attenuated VILI. Collectively, these results suggested that CXCL14 overexpression attenuates VILI through the downregulation of PKM2-mediated proinflammatory cytokine production.

Citing Articles

Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization.

Luo J, Wang J, Zhang J, Sang A, Ye X, Cheng Z Cells. 2022; 11(23).

PMID: 36497185 PMC: 9735993. DOI: 10.3390/cells11233927.

Role of PKM2-Mediated Immunometabolic Reprogramming on Development of Cytokine Storm.

Liu Z, Le Y, Chen H, Zhu J, Lu D Front Immunol. 2021; 12:748573.

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YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization.

Luo Q, Luo J, Wang Y J Inflamm Res. 2021; 13:1279-1290.

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References

Hu K, Yang Y, Lin L, Ai Q, Dai J, Fan K . Caloric Restriction Mimetic 2-Deoxyglucose Alleviated Inflammatory Lung Injury Suppressing Nuclear Pyruvate Kinase M2-Signal Transducer and Activator of Transcription 3 Pathway. Front Immunol. 2018; 9:426. PMC: 5840172. DOI: 10.3389/fimmu.2018.00426. View

Lu J, Song G, Tang Q, Zou C, Han F, Zhao Z . IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling. J Clin Invest. 2015; 125(5):1839-56. PMC: 4463198. DOI: 10.1172/JCI78437. View

Tsaknis G, Siempos I, Kopterides P, Maniatis N, Magkou C, Kardara M . Metformin attenuates ventilator-induced lung injury. Crit Care. 2012; 16(4):R134. PMC: 3580719. DOI: 10.1186/cc11439. View

Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X . Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene. 2011; 30(42):4297-306. DOI: 10.1038/onc.2011.137. View

Ware L, Matthay M . The acute respiratory distress syndrome. N Engl J Med. 2000; 342(18):1334-49. DOI: 10.1056/NEJM200005043421806. View

Zhong W, Yang H, Guan X, Xiong J, Sun C, Zhang C . Inhibition of glycolysis alleviates lipopolysaccharide-induced acute lung injury in a mouse model. J Cell Physiol. 2018; 234(4):4641-4654. DOI: 10.1002/jcp.27261. View

Yang W, Xia Y, Ji H, Zheng Y, Liang J, Huang W . Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature. 2011; 480(7375):118-22. PMC: 3235705. DOI: 10.1038/nature10598. View

Park I, Mukherjee J, Ito M, Chaumeil M, Jalbert L, Gaensler K . Changes in pyruvate metabolism detected by magnetic resonance imaging are linked to DNA damage and serve as a sensor of temozolomide response in glioblastoma cells. Cancer Res. 2014; 74(23):7115-24. PMC: 4253720. DOI: 10.1158/0008-5472.CAN-14-0849. View

Xie M, Yu Y, Kang R, Zhu S, Yang L, Zeng L . PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nat Commun. 2016; 7:13280. PMC: 5093342. DOI: 10.1038/ncomms13280. View

10.

Wallace M, Probyn M, Zahra V, Crossley K, Cole T, Davis P . Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs. Respir Res. 2009; 10:19. PMC: 2662809. DOI: 10.1186/1465-9921-10-19. View

11.

Chen J, Jiang Z, Wang B, Wang Y, Hu X . Vitamin K(3) and K(5) are inhibitors of tumor pyruvate kinase M2. Cancer Lett. 2011; 316(2):204-10. DOI: 10.1016/j.canlet.2011.10.039. View

12.

Lu J, Chatterjee M, Schmid H, Beck S, Gawaz M . CXCL14 as an emerging immune and inflammatory modulator. J Inflamm (Lond). 2016; 13:1. PMC: 4700668. DOI: 10.1186/s12950-015-0109-9. View

13.

Maerki C, Meuter S, Liebi M, Muhlemann K, Frederick M, Yawalkar N . Potent and broad-spectrum antimicrobial activity of CXCL14 suggests an immediate role in skin infections. J Immunol. 2008; 182(1):507-14. DOI: 10.4049/jimmunol.182.1.507. View

14.

Salvesen O, Reiten M, Espenes A, Bakkebo M, Tranulis M, Ersdal C . LPS-induced systemic inflammation reveals an immunomodulatory role for the prion protein at the blood-brain interface. J Neuroinflammation. 2017; 14(1):106. PMC: 5441080. DOI: 10.1186/s12974-017-0879-5. View

15.

Kaner R, Ladetto J, Singh R, Fukuda N, Matthay M, Crystal R . Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol Biol. 2000; 22(6):657-64. DOI: 10.1165/ajrcmb.22.6.3779. View

16.

Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F . PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation. Mol Cancer. 2016; 15:3. PMC: 4704385. DOI: 10.1186/s12943-015-0490-2. View

17.

Wang T, Gross C, Desai A, Zemskov E, Wu X, Garcia A . Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets. Am J Physiol Lung Cell Mol Physiol. 2016; 312(4):L452-L476. PMC: 5407098. DOI: 10.1152/ajplung.00231.2016. View

18.

Frick I, Nordin S, Baumgarten M, Morgelin M, Sorensen O, Olin A . Constitutive and inflammation-dependent antimicrobial peptides produced by epithelium are differentially processed and inactivated by the commensal Finegoldia magna and the pathogen Streptococcus pyogenes. J Immunol. 2011; 187(8):4300-9. DOI: 10.4049/jimmunol.1004179. View

19.

Dai C, Basilico P, Cremona T, Collins P, Moser B, Benarafa C . CXCL14 displays antimicrobial activity against respiratory tract bacteria and contributes to clearance of Streptococcus pneumoniae pulmonary infection. J Immunol. 2015; 194(12):5980-9. DOI: 10.4049/jimmunol.1402634. View

20.

Zhang Y, Liu X, Zhang X, Zhang J . Shikonin improve sepsis-induced lung injury via regulation of miRNA-140-5p/TLR4-a vitro and vivo study. J Cell Biochem. 2019; 121(3):2103-2117. DOI: 10.1002/jcb.28199. View