Maresin 1 Maintains the Permeability of Lung Epithelial Cells In Vitro and In Vivo
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Previous reports showed that Maresin 1 (MaR1) possessed organ protection effects and could attenuate acute lung injury. Here, we aim to figure out whether MaR1 can maintain the permeability of lung epithelial cells by regulating the expression of tight junction protein during lung injury. Monolayer of murine lung epithelial cells was stimulated by lipopolysaccharide (LPS) with or without MaR1 and the permeability was evaluated. The expression of Claudin-1 and ZO-1 in lung epithelial cells was analyzed by immunofluorescence staining and western blotting. MaR1 was given to the mice after LPS induced acute lung injury. The permeability of lung was assessed by Evans Blue extravasation, lung wet/dry ratio and protein concentration in bronchoalveolar lavage fluid. Lung injury score was also evaluated. The expression of Claudin-1 and ZO-1 in the lung was analyzed by immunofluorescence staining. Results showed that MaR1 maintained the permeability of lung epithelial cells and upregulated the expression of Claudin-1 and ZO-1 after LPS stimulation. In acute lung injury mice, MaR1 upregulated the expression of Claudin-1 and ZO-1, decreased lung permeability, and reduced lung injury. In summary, this study suggests that MaR1 can maintain the permeability of lung epithelial cells by upregulating the expression of Claudin-1 and ZO-1 in acute lung injury.
KEY WORDSMaresin 1 lipopolysaccharide acute lung injury tight junction permeability
This study was supported by grants from the National Natural Science Foundation of China (No. 30930089, 81372036, 81500064, 81671890,81601669 ) and Key Clinical Project of Ministry of Health of China (2012-47).
L.C. and H.L. performed the research and wrote the manuscript. Y.W. and H.X. performed the in vitro study. J.G. and B.L. carried out the animal experiment and analyzed the data. S.Y. and Y.S. designed the experiment and revised the paper.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 8.Miyoshi, K., S. Yanagi, K. Kawahara, M. Nishio, H. Tsubouchi, Y. Imazu, R. Koshida, N. Matsumoto, A. Taguchi, S. Yamashita, A. Suzuki, and M. Nakazato. 2013. Epithelial Pten controls acute lung injury and fibrosis by regulating alveolar epithelial cell integrity. American Journal of Respiratory and Critical Care Medicine 187: 262–275.CrossRefPubMedGoogle Scholar
- 10.Borgeson, E., A.M. Johnson, Y.S. Lee, A. Till, G.H. Syed, S.T. Ali-Shah, P.J. Guiry, J. Dalli, R.A. Colas, C.N. Serhan, K. Sharma, and C. Godson. 2015. Lipoxin A4 attenuates obesity-induced adipose inflammation and associated liver and kidney disease. Cell Metabolism 22: 125–137.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Kain, V., K.A. Ingle, R.A. Colas, J. Dalli, S.D. Prabhu, C.N. Serhan, M. Joshi, and G.V. Halade. 2015. Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function. Journal of Molecular and Cellular Cardiology 84: 24–35.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Krishnamoorthy, N., P.R. Burkett, J. Dalli, R.E. Abdulnour, R. Colas, S. Ramon, R.P. Phipps, N.A. Petasis, V.K. Kuchroo, C.N. Serhan, and B.D. Levy. 2015. Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation. Journal of Immunology 194: 863–867.CrossRefGoogle Scholar
- 18.Gong, J., H. Liu, J. Wu, H. Qi, Z.Y. Wu, H.Q. Shu, H.B. Li, L. Chen, Y.X. Wang, B. Li, M. Tang, Y.D. Ji, S.Y. Yuan, S.L. Yao, and Y. Shang. 2015. Maresin 1 prevents lipopolysaccharide-induced neutrophil survival and accelerates resolution of acute lung injury. Shock 44: 371–380.CrossRefPubMedGoogle Scholar
- 19.Wang, Y., R. Li, L. Chen, W. Tan, Z. Sun, H. Xia, B. Li, Y. Yu, J. Gong, M. Tang, Y. Ji, S. Yuan, Shanglong Yao, and Y. Shang. 2015. Maresin 1 inhibits epithelial-to-mesenchymal transition in vitro and attenuates bleomycin induced lung fibrosis in vivo. Shock 44: 496–502.CrossRefPubMedGoogle Scholar
- 21.Matute-Bello, G., G. Downey, B.B. Moore, S.D. Groshong, M.A. Matthay, A.S. Slutsky, W.M. Kuebler, and Acute Lung Injury in Animals Study Group. 2011. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. American Journal of Respiratory Cell and Molecular Biology 44: 725–738.CrossRefPubMedGoogle Scholar
- 22.Abdulnour, R.E., J. Dalli, J.K. Colby, N. Krishnamoorthy, J.Y. Timmons, S.H. Tan, R.A. Colas, N.A. Petasis, C.N. Serhan, and B.D. Levy. 2014. Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective. Proceedings of the National Academy of Science 111: 16526–16531.CrossRefGoogle Scholar
- 26.Broermann, A., M. Winderlich, H. Block, M. Frye, J. Rossaint, A. Zarbock, G. Cagna, R. Linnepe, D. Schulte, A.F. Nottebaum, and D. Vestweber. 2011. Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo. The Journal of Experimental Medicine 208: 2393–2401.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Fang, X., A.P. Neyrinck, M.A. Matthay, and J.W. Lee. 2010. Allogeneic human mesenchymal stem cells restore epithelial protein permeability in cultured human alveolar type II cells by secretion of angiopoietin-1. The Journal of Biological Chemistry 285: 26211–26222.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Schamberger, A.C., N. Mise, J. Jia, E. Genoyer, A.O. Yildirim, S. Meiners, and O. Eickelberg. 2014. Cigarette smoke-induced disruption of bronchial epithelial tight junctions is prevented by transforming growth factor-beta. American Journal of Respiratory Cell and Molecular Biology 50: 1040–1052.CrossRefPubMedGoogle Scholar
- 35.Englert, J.A., A.A. Macias, D. Amador-Munoz, M. Pinilla Vera, C. Isabelle, J. Guan, B. Magaoay, M. Suarez Velandia, A. Coronata, A. Lee, L.E. Fredenburgh, D.J. Culley, G. Crosby, and R.M. Baron. 2015. Isoflurane ameliorates acute lung injury by preserving epithelial tight junction integrity. Anesthesiology 123: 377–388.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.LaFemina, M.J., K.M. Sutherland, T. Bentley, L.W. Gonzales, L. Allen, C.J. Chapin, D. Rokkam, K.A. Sweerus, L.G. Dobbs, P.L. Ballard, and J.A. Frank. 2014. Claudin-18 deficiency results in alveolar barrier dysfunction and impaired alveologenesis in mice. American Journal of Respiratory Cell and Molecular Biology 51: 550–558.CrossRefPubMedPubMedCentralGoogle Scholar
- 39.Cording, J., J. Berg, N. Kading, C. Bellmann, C. Tscheik, J.K. Westphal, S. Milatz, D. Günzel, H. Wolburg, J. Piontek, O. Huber, and I.E. Blasig. 2013. In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization. Journal of Cell Science 126: 554–564.CrossRefPubMedGoogle Scholar
- 41.Ragupathy, S., F. Esmaeili, S. Paschoud, E. Sublet, S. Citi, and G. Borchard. 2014. Toll-like receptor 2 regulates the barrier function of human bronchial epithelial monolayers through atypical protein kinase C zeta, and an increase in expression of claudin-1. Tissue Barriers 2: e29166.CrossRefPubMedPubMedCentralGoogle Scholar