Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
July-2020 Volume 22 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2020 Volume 22 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells

  • Authors:
    • Yuntao Zhang
    • Wang Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 534-542
    |
    Published online on: May 4, 2020
       https://doi.org/10.3892/mmr.2020.11109
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Pulmonary epithelial barrier dysfunction is a critical pathological component of lung injury, caused primarily by impaired epithelial cell migration. Moreover, macrophage‑epithelial interactions in pulmonary alveoli may either protect or damage epithelial barrier function. To investigate the effects of different macrophage subtypes, M1 and M2, on lipopolysaccharide (LPS)‑induced epithelial barrier dysfunction, M1 and M2 macrophages were used to treat LPS‑injured musculus lung epithelial cells (MLE‑12). Barrier function was evaluated by monitoring cell monolayer permeability, T‑cell immunoglobulin mucin 3 (Tim‑3) small interfering RNA and anti‑mouse Tim‑3 antibody were used to knockdown or block endogenous Tim‑3, to verify the role of the Tim‑3 in macrophage‑mediated barrier protection in LPS‑injured MLE‑12 cells. LY294002 was used to inhibit the activity of PI3K to verify the role of the PI3K/Akt signaling pathway in the restoration of epithelial cell. The present results revealed that co‑culture of LPS‑treated epithelial MLE‑12 cells with M1 macrophages decreased cell migration and promoted permeability, whereas co‑culture with M2 macrophages caused the opposite effects. It was determined that blocking T‑cell immunoglobulin mucin 3 (Tim‑3) signaling in macrophages and PI3K/Akt signaling in epithelial cells eliminated the barrier protection supplied by M2 macrophages. Tim‑3, which maintains macrophage M2 polarization, is a key component of the macrophage‑mediated barrier‑repair process, while M2 macrophages regulate PI3K/Akt signaling in epithelial cells, which in turn enhances pulmonary epithelial barrier function by restoring cell migration.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Brune K, Frank J, Schwingshackl A, Finigan J and Sidhaye V: Pulmonary epithelial barrier function: Some new players and mechanisms. Am J Physiol Lung Cell Mol Physiol. 308:L731–L745. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Gunther J and Seyfert HM: The first line of defence: Insights into mechanisms and relevance of phagocytosis in epithelial cells. Semin Immunopathol. 40:555–565. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Guillot L, Nathan N, Tabary O, Thouvenin G, Le Rouzic P, Corvol H, Amselem S and Clement A: Alveolar epithelial cells: Master regulators of lung homeostasis. Int J Biochem Cell Biol. 45:2568–2573. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Bhattacharya JK: Westphalen, Macrophage-epithelial interactions in pulmonary alveoli. Semin Immunopathol. 38:461–469. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Rodgers LS and Fanning AS: Regulation of epithelial permeability by the actin cytoskeleton. Cytoskeleton (Hoboken, N.J.). 68:653–660. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Herold S, Gabrielli NM and Vadasz I: Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction. Am J Physiol Lung Cell Mol Physiol. 305:L665–L681. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Wang W, Weng J, Yu L, Huang Q, Jiang Y and Guo X: Role of TLR4-p38 MAPK-Hsp27 signal pathway in LPS-induced pulmonary epithelial hyperpermeability. BMC Pulm Med. 18:1782018. View Article : Google Scholar : PubMed/NCBI

8 

Zheng X, Zhang W and Hu X: Different concentrations of lipopolysaccharide regulate barrier function through the PI3K/Akt signalling pathway in human pulmonary microvascular endothelial cells. Sci Rep. 8:99632018. View Article : Google Scholar : PubMed/NCBI

9 

Geiser T: Mechanisms of alveolar epithelial repair in acute lung injury-a translational approach. Swiss Med Wkly. 133:586–590. 2003.PubMed/NCBI

10 

Nova Z, Skovierova H and Calkovska A: Alveolar-capillary membrane-related pulmonary cells as a target in endotoxin-induced acute lung injury. Int J Mol Sci. 20(pii): E8312019. View Article : Google Scholar : PubMed/NCBI

11 

Reynier F, de Vos AF, Hoogerwerf JJ, Bresser P, van der Zee JS, Paye M, Pachot A, Mougin B and van der Poll T: Gene expression profiles in alveolar macrophages induced by lipopolysaccharide in humans. Mol Med. 18:1303–1311. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Aggarwal NR, King LS and D'Alessio FR: Diverse macrophage populations mediate acute lung inflammation and resolution. Am J Physiol Lung Cell Mol Physiol. 306:L709–L275. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Xia Q, Wei L and Zhang Y, Sheng J, Wu W and Zhang Y: Immune checkpoint receptors Tim-3 and PD-1 regulate monocyte and T Lymphocyte function in septic patients. Mediators Inflamm. 2018:16329022018. View Article : Google Scholar : PubMed/NCBI

14 

Zhang W, Zhang Y, He Y, Wang X and Fang Q: Lipopolysaccharide mediates time-dependent macrophage M1/M2 polarization through the Tim-3/Galectin-9 signalling pathway. Exp Cell Res. 376:124–132. 2019. View Article : Google Scholar : PubMed/NCBI

15 

Hunter MM, Wang A, Parhar KS, Johnston MJ, Van Rooijen N, Beck PL and McKay DM: In vitro-derived alternatively activated macrophages reduce colonic inflammation in mice. Gastroenterology. 138:1395–1405. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Patterson CE, Rhoades RA and Garcia JG: Evans blue dye as a marker of albumin clearance in cultured endothelial monolayer and isolated lung. J Appl Physiol (1985). 72:865–873. 1992. View Article : Google Scholar : PubMed/NCBI

18 

Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ and Hudson LD: Incidence and outcomes of acute lung injury. N Engl J Med. 353:1685–1693. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Ellison RT III and Giehl TJ: Killing of gram-negative bacteria by lactoferrin and lysozyme. J Clin Invest. 88:1080–1091. 1991. View Article : Google Scholar : PubMed/NCBI

20 

Ibrahim HR, Aoki T and Pellegrini A: Strategies for new antimicrobial proteins and peptides: Lysozyme and aprotinin as model molecules. Curr Pharm Des. 8:671–693. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Hamacher J, Hadizamani Y, Borgmann M, Mohaupt M, Männel DN, Moehrlen U, Lucas R and Stammberger U: Cytokine-Ion channel interactions in pulmonary inflammation. Front Immunol. 8:16442017. View Article : Google Scholar : PubMed/NCBI

22 

Ito Y, Correll K, Schiel JA, Finigan JH, Prekeris R and Mason RJ: Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling. Am J Physiol Lung Cell Mol Physiol. 307:L94–L105. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Lindsay CD: Novel therapeutic strategies for acute lung injury induced by lung damaging agents: The potential role of growth factors as treatment options. Hum Exp Toxicol. 30:701–724. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Du Z, Zhang S, Lin Y, Zhou L, Wang Y, Yan G, Zhang M, Wang M, Li J, Tong Q, et al: Momordicoside G Regulates macrophage phenotypes to stimulate efficient repair of lung injury and prevent urethane-induced lung carcinoma lesions. Front Pharmacol. 10:3212019. View Article : Google Scholar : PubMed/NCBI

25 

Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, Manning S, Greenfield EA, Coyle AJ, Sobel RA, et al: Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 415:536–541. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Sabatos CA, Chakravarti S, Cha E, Schubart A, Sánchez-Fueyo A, Zheng XX, Coyle AJ, Strom TB, Freeman GJ and Kuchroo VK: Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol. 4:1102–1110. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Liu X, Jiang S, Zhang Q, Xu S, Bao X, Cao W, Bai J and Tang L: Tim-3 regulates Tregs' ability to resolve the inflammation and proliferation of acute lung injury by modulating macrophages polarization. Shock. 50:455–464. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Yang X, Jiang X, Chen G, Xiao Y, Geng S, Kang C, Zhou T, Li Y, Guo X, Xiao H, et al: T cell Ig mucin-3 promotes homeostasis of sepsis by negatively regulating the TLR response. J Immunol. 190:2068–2079. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Xu X, Li H, Gong Y, Zheng H and Zhao D: Hydrogen sulfide ameliorated lipopolysaccharide-induced acute lung injury by inhibiting autophagy through PI3K/Akt/mTOR pathway in mice. Biochem Biophys Res Commun. 507:514–518. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Wu XT, Ansari AR, Pang XX, Li HZ, Zhang ZW, Luo Y, Arshad M and Song H: Visfatin plays a significant role in alleviating lipopolysaccharide-induced apoptosis and autophagy through PI3K/AKT signaling pathway during acute lung injury in mice. Arch Immunol Ther Exp (Warsz). 67:249–261. 2019. View Article : Google Scholar : PubMed/NCBI

31 

Brazil JC, Quiros M, Nusrat A and Parkos CA: Innate immune cell-epithelial crosstalk during wound repair. J Clin Invest. 129:2983–2993. 2019. View Article : Google Scholar : PubMed/NCBI

32 

Saraiva M, Vieira P and O'Garra A: Biology and therapeutic potential of interleukin-10. J Exp Med. 217(pii): e201904182019.

33 

Kim SY, Joglekar MV, Hardikar AA, Phan TH, Khanal D, Tharkar P, Limantoro C, Johnson J, Kalionis B and Chrzanowski W: Placenta Stem/Stromal cell-derived extracellular vesicles for potential use in lung repair. Proteomics. 19:e18001662019. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang Y and Zhang W: Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells. Mol Med Rep 22: 534-542, 2020.
APA
Zhang, Y., & Zhang, W. (2020). Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells. Molecular Medicine Reports, 22, 534-542. https://doi.org/10.3892/mmr.2020.11109
MLA
Zhang, Y., Zhang, W."Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells". Molecular Medicine Reports 22.1 (2020): 534-542.
Chicago
Zhang, Y., Zhang, W."Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells". Molecular Medicine Reports 22, no. 1 (2020): 534-542. https://doi.org/10.3892/mmr.2020.11109
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y and Zhang W: Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells. Mol Med Rep 22: 534-542, 2020.
APA
Zhang, Y., & Zhang, W. (2020). Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells. Molecular Medicine Reports, 22, 534-542. https://doi.org/10.3892/mmr.2020.11109
MLA
Zhang, Y., Zhang, W."Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells". Molecular Medicine Reports 22.1 (2020): 534-542.
Chicago
Zhang, Y., Zhang, W."Tim‑3 regulates the ability of macrophages to counter lipopolysaccharide‑induced pulmonary epithelial barrier dysfunction via the PI3K/Akt pathway in epithelial cells". Molecular Medicine Reports 22, no. 1 (2020): 534-542. https://doi.org/10.3892/mmr.2020.11109
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team