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Inflammation Research

Erschienen in:

13.11.2020 | Original Research Paper

PIM1 inhibition attenuated endotoxin-induced acute lung injury through modulating ELK3/ICAM1 axis on pulmonary microvascular endothelial cells

verfasst von: Yumeng Cao, Xia Chen, Yuqi Liu, Xingyi Zhang, Yun Zou, Jinbao Li

Erschienen in: Inflammation Research | Ausgabe 1/2021

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Abstract

Objective

The dysfunction of pulmonary microvascular endothelial cells (PMVECs) is one of the critical characteristics of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) induced by severe infection. PIM1 is a constitutively active serine/threonine kinase that is involved in multiple biological processes. However, the underlying correlation between PIM1 and PMVECs injury remains unclear. The main purpose of this study was to reveal roles of PIM1 and explore the potential mechanisms during the development of endotoxin-induced ALI induced by intraperitoneal LPS administration.

Materials and methods

PIM1 level in the lung tissues of endotoxin-induced ALI mice or plasma derived from cardiopulmonary bypass (CPB)-induced ALI patients were measured. The protective roles of PIM1 specific inhibitor SMI-4a on endotoxin-induced lung injuries were evaluated through histological, permeability, neutrophil infiltration and survival assessment. The relationship between PIM1 and ELK3/ICAM-1 axis was validated in vivo and vitro. The correlation between plasma PIM1 and indicative vascular endothelium injury biomarkers (PaO₂/FiO₂ ratio, Ang-II, E-selectin and PAI-1) levels derived from CPB-induced ALI patient were analyzed.

Results

PIM1 expression in the lung tissues was increased in the mice of endotoxin-induced ALI. The PIM1 specific inhibitor SMI-4a administration relieved the severity of endotoxin-induced ALI. More importantly, PIM1 modulates ICAM1 expression through regulating transcription factor ELK3 expression in vitro. Eventually, plasma PIM1 level was positively correlated with Ang-II and PAI-1 levels but negatively correlated with SpO₂/FiO₂ ratio among CPB induced ALI patients.

Conclusion

Our results indicated that PIM1 inhibition carried a protective role against endotoxin-induced ALI by modulating the ELK3/ICAM1 axis on PMVECs. PIM1 may be a potential therapeutic target for endotoxin-induced ALI.

Nur mit Berechtigung zugänglich

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10. https://doi.org/10.1001/jama.2016.0287.PubMedPubMedCentralCrossRef

Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019;5(1):18. https://doi.org/10.1038/s41572-019-0069-0.PubMedPubMedCentralCrossRef

Pham T, Rubenfeld GD. Fifty years of research in ARDS. The epidemiology of acute respiratory distress syndrome. A 50th birthday review. Am J Respir Crit Care Med. 2017;195(7):860–70. https://doi.org/10.1164/rccm.201609-1773CP.PubMedCrossRef

Matthay MA, McAuley DF, Ware LB. Clinical trials in acute respiratory distress syndrome: challenges and opportunities. Lancet Respir Med. 2017;5(6):524–34. https://doi.org/10.1016/S2213-2600(17)30188-1.PubMedCrossRef

Fanelli V, Ranieri VM. Mechanisms and clinical consequences of acute lung injury. Ann Am Thorac Soc. 2015;12(Suppl 1):S3-8. https://doi.org/10.1513/AnnalsATS.201407-340MG.PubMedCrossRef

Bachofen M, Weibel ER. Structural alterations of lung parenchyma in the adult respiratory distress syndrome. Clin Chest Med. 1982;3(1):35–56.PubMed

Park I, Kim M, Choe K, Song E, Seo H, Hwang Y, et al. Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury. Eur Respir J. 2019. https://doi.org/10.1183/13993003.00786-2018.PubMedPubMedCentralCrossRef

Li H, Hao Y, Yang LL, Wang XY, Li XY, Bhandari S, et al. MCTR1 alleviates lipopolysaccharide-induced acute lung injury by protecting lung endothelial glycocalyx. J Cell Physiol. 2020. https://doi.org/10.1002/jcp.29628.PubMedPubMedCentralCrossRef

Bhattacharya J, Matthay MA. Regulation and repair of the alveolar-capillary barrier in acute lung injury. Annu Rev Physiol. 2013;75:593–615. https://doi.org/10.1146/annurev-physiol-030212-183756.PubMedCrossRef

10.

Minamino T, Komuro I. Regeneration of the endothelium as a novel therapeutic strategy for acute lung injury. J Clin Investig. 2006;116(9):2316–9. https://doi.org/10.1172/JCI29637.PubMedCrossRefPubMedCentral

11.

Zhu X, Zou Y, Wang B, Zhu J, Chen Y, Wang L, et al. Blockade of CXC chemokine receptor 3 on endothelial cells protects against sepsis-induced acute lung injury. J Surg Res. 2016;204(2):288–96. https://doi.org/10.1016/j.jss.2016.04.067.PubMedCrossRef

12.

Huertas A, Guignabert C, Barbera JA, Bartsch P, Bhattacharya J, Bhattacharya S, et al. Pulmonary vascular endothelium: the orchestra conductor in respiratory diseases: highlights from basic research to therapy. Eur Respir J. 2018. https://doi.org/10.1183/13993003.00745-2017.PubMedCrossRef

13.

Zou Y, Bao S, Wang F, Guo L, Zhu J, Wang J, et al. FN14 blockade on pulmonary microvascular endothelial cells improves the outcome of sepsis-induced acute lung injury. Shock. 2018;49(2):213–20. https://doi.org/10.1097/SHK.0000000000000915.PubMedCrossRef

14.

Braso-Maristany F, Filosto S, Catchpole S, Marlow R, Quist J, Francesch-Domenech E, et al. PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Nat Med. 2016;22(11):1303–13. https://doi.org/10.1038/nm.4198.PubMedPubMedCentralCrossRef

15.

Aho TL, Sandholm J, Peltola KJ, Mankonen HP, Lilly M, Koskinen PJ. Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site. FEBS Lett. 2004;571(1–3):43–9. https://doi.org/10.1016/j.febslet.2004.06.050.PubMedCrossRef

16.

Bhattacharya N, Wang Z, Davitt C, McKenzie IF, Xing PX, Magnuson NS. Pim-1 associates with protein complexes necessary for mitosis. Chromosoma. 2002;111(2):80–95. https://doi.org/10.1007/s00412-002-0192-6.PubMedCrossRef

17.

Saris CJ, Domen J, Berns A. The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG. EMBO J. 1991;10(3):655–64.PubMedPubMedCentralCrossRef

18.

Asati V, Mahapatra DK, Bharti SK. PIM kinase inhibitors: structural and pharmacological perspectives. Eur J Med Chem. 2019;172:95–108. https://doi.org/10.1016/j.ejmech.2019.03.050.PubMedCrossRef

19.

Katsube A, Hayashi H, Kusuhara H. Pim-1L protects cell surface-resident ABCA1 from lysosomal degradation in hepatocytes and thereby regulates plasma high-density lipoprotein level. Arterioscler Thromb Vasc Biol. 2016;36(12):2304–14. https://doi.org/10.1161/ATVBAHA.116.308472.PubMedCrossRef

20.

Xie Y, Xu K, Linn DE, Yang X, Guo Z, Shimelis H, et al. The 44-kDa Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells. J Biol Chem. 2008;283(6):3349–56. https://doi.org/10.1074/jbc.M707773200.PubMedCrossRef

21.

Bitrian V, Trullas J. Molecular dynamics study of polarizable ion models for molten AgBr. J Phys Chem B. 2006;110(14):7490–9. https://doi.org/10.1021/jp056818u.PubMedCrossRef

22.

Zhao W, Qiu R, Li P, Yang J. PIM1: a promising target in patients with triple-negative breast cancer. Med Oncol. 2017;34(8):142. https://doi.org/10.1007/s12032-017-0998-y.PubMedCrossRef

23.

Narlik-Grassow M, Blanco-Aparicio C, Carnero A. The PIM family of serine/threonine kinases in cancer. Med Res Rev. 2014;34(1):136–59. https://doi.org/10.1002/med.21284.PubMedCrossRef

24.

Kim K, Kim JH, Youn BU, Jin HM, Kim N. Pim-1 regulates RANKL-induced osteoclastogenesis via NF-kappaB activation and NFATc1 induction. J Immunol. 2010;185(12):7460–6. https://doi.org/10.4049/jimmunol.1000885.PubMedCrossRef

25.

Lim R, Barker G, Lappas M. Inhibition of PIM1 kinase attenuates inflammation-induced pro-labour mediators in human foetal membranes in vitro. Mol Hum Reprod. 2017;23(6):428–40. https://doi.org/10.1093/molehr/gax013.PubMedCrossRef

26.

Wang J, Cao Y, Liu Y, Zhang X, Ji F, Li J, et al. PIM1 inhibitor SMI-4a attenuated lipopolysaccharide-induced acute lung injury through suppressing macrophage inflammatory responses via modulating p65 phosphorylation. Int Immunopharmacol. 2019;73:568–74. https://doi.org/10.1016/j.intimp.2019.05.040.PubMedCrossRef

27.

Zou Y, Cao Y, Liu Y, Zhang X, Li J, Xiong Y. The role of dorsal root ganglia PIM1 in peripheral nerve injury-induced neuropathic pain. Neurosci Lett. 2019;709:134375. https://doi.org/10.1016/j.neulet.2019.134375.PubMedCrossRef

28.

Singh N, Li L. Reduced oxidative tissue damage during endotoxemia in IRAK-1 deficient mice. Mol Immunol. 2012;50(4):244–52. https://doi.org/10.1016/j.molimm.2012.01.011.PubMedPubMedCentralCrossRef

29.

Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS, et al. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011;44(5):725–38. https://doi.org/10.1165/rcmb.2009-0210ST.PubMedPubMedCentralCrossRef

30.

Radu M, Chernoff J. An in vivo assay to test blood vessel permeability. J Vis Exp. 2013;73:e50062. https://doi.org/10.3791/50062.CrossRef

31.

Xing Z, Han J, Hao X, Wang J, Jiang C, Hao Y, et al. Immature monocytes contribute to cardiopulmonary bypass-induced acute lung injury by generating inflammatory descendants. Thorax. 2017;72(3):245–55. https://doi.org/10.1136/thoraxjnl-2015-208023.PubMedCrossRef

32.

Carney DE, Lutz CJ, Picone AL, Gatto LA, Ramamurthy NS, Golub LM, et al. Matrix metalloproteinase inhibitor prevents acute lung injury after cardiopulmonary bypass. Circulation. 1999;100(4):400–6. https://doi.org/10.1161/01.cir.100.4.400.PubMedCrossRef

33.

Chen X, Jiang J, Wu X, Li J, Li S. Plasma Cold-Inducible RNA-binding protein predicts lung dysfunction after cardiovascular surgery following cardiopulmonary bypass: a prospective observational study. Med Sci Monit. 2019;25:3288–97. https://doi.org/10.12659/MSM.914318.PubMedPubMedCentralCrossRef

34.

Matthay MA, Zemans RL. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol. 2011;6:147–63. https://doi.org/10.1146/annurev-pathol-011110-130158.PubMedPubMedCentralCrossRef

35.

Donnelly SC, Haslett C, Dransfield I, Robertson CE, Carter DC, Ross JA, et al. Role of selectins in development of adult respiratory distress syndrome. Lancet. 1994;344(8917):215–9. https://doi.org/10.1016/s0140-6736(94)92995-5.PubMedCrossRef

36.

Hu G, Vogel SM, Schwartz DE, Malik AB, Minshall RD. Intercellular adhesion molecule-1-dependent neutrophil adhesion to endothelial cells induces caveolae-mediated pulmonary vascular hyperpermeability. Circ Res. 2008;102(12):e120–31. https://doi.org/10.1161/CIRCRESAHA.107.167486.PubMedPubMedCentralCrossRef

37.

Tan WSD, Liao W, Zhou S, Mei D, Wong WF. Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases. Curr Opin Pharmacol. 2018;40:9–17. https://doi.org/10.1016/j.coph.2017.12.002.PubMedCrossRef

38.

Chen YH, Layne MD, Chung SW, Ejima K, Baron RM, Yet SF, et al. Elk-3 is a transcriptional repressor of nitric-oxide synthase 2. J Biol Chem. 2003;278(41):39572–7. https://doi.org/10.1074/jbc.M308179200.PubMedCrossRef

39.

Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, et al. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007;116(17):1896–906. https://doi.org/10.1161/CIRCULATIONAHA.106.684852.PubMedCrossRef

Titel: PIM1 inhibition attenuated endotoxin-induced acute lung injury through modulating ELK3/ICAM1 axis on pulmonary microvascular endothelial cells
verfasst von: Yumeng Cao
Xia Chen
Yuqi Liu
Xingyi Zhang
Yun Zou
Jinbao Li
Publikationsdatum: 13.11.2020
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 1/2021
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-020-01420-3

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PIM1 inhibition attenuated endotoxin-induced acute lung injury through modulating ELK3/ICAM1 axis on pulmonary microvascular endothelial cells

Abstract

Objective

Materials and methods

Results

Conclusion

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