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
January-2018 Volume 17 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
January-2018 Volume 17 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
Article Open Access

TIPE2 governs macrophage polarization via negative regulation of mTORC1

  • Authors:
    • Yuan Jiang
    • Qiang Li
    • Yuanyuan Zhang
    • Yuzhi Gao
    • Libing Jiang
    • Zhimin Chen
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310051, P.R. China, Emergency Department, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 952-960
    |
    Published online on: November 6, 2017
       https://doi.org/10.3892/mmr.2017.7991
  • 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

Macrophages can be polarized into the inflammatory M1 lineage or the immunomodulatory M2 lineage, depending on the differential tissue microenvironment signaling, specific pathogens or cytokine stimulation. Tumor necrosis factor α‑induced protein 8‑like protein 2 (TIPE2) has been demonstrated to negatively regulate inflammation by inhibiting the Toll‑like receptor (TLR) pathway. The present study utilized murine bone marrow derived macrophages (BMDMs) as the model of undifferentiated (M0) macrophages to study the roles of TIPE2 in the differential polarization status of BMDMs. It was observed that the expression levels of TIPE2 were diminished in M1 macrophages treated with lipopolysaccharide/interferon γ, and elevated in M2 macrophages treated with interleukin (IL)‑4. BMDMs with TIPE2 overexpression exhibited defective M1 polarization and enhanced responses to IL‑4 stimulation. TIPE2 impeded M1 polarization by interfering with mitogen‑activated protein kinase kinase kinase 7‑inhibitor of nuclear factor‑κB kinase subunit β and B cell receptor‑associated protein‑serine/threonine‑protein kinase mTOR complex 1 (mTORC1) activation. TIPE2 overexpression accelerated IL‑4 induced M2 polarization by dampening mTORC1 activation via the accelerated process of arginine to urea. Overall, these results define a key role for TIPE2 in macrophage polarization by impeding mTORC1 response.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Mosser DM and Edwards JP: Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 8:958–969. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Ginhoux F and Jung S: Monocytes and macrophages: Developmental pathways and tissue homeostasis. Nat Rev Immunol. 14:392–404. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Varol C, Mildner A and Jung S: Macrophages: Development and tissue specialization. Annu Rev Immunol. 33:643–675. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Italiani P and Boraschi D: From Monocytes to M1/M2 Macrophages: Phenotypical vs. functional differentiation. Front Immunol. 5:5142014. View Article : Google Scholar : PubMed/NCBI

5 

Saeed S, Quintin J, Kerstens HH, Rao NA, Aghajanirefah A, Matarese F, Cheng SC, Ratter J, Berentsen K, van der Ent MA, et al: Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science. 345:12510862014. View Article : Google Scholar : PubMed/NCBI

6 

Byles V, Covarrubias AJ, Ben-Sahra I, Lamming DW, Sabatini DM, Manning BD and Horng T: The TSC-mTOR pathway regulates macrophage polarization. Nat Commun. 4:28342013. View Article : Google Scholar : PubMed/NCBI

7 

Covarrubias AJ, Aksoylar HI and Horng T: Control of macrophage metabolism and activation by mTOR and Akt signaling. Semin Immunol. 27:286–296. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Weichhart T, Hengstschläger M and Linke M: Regulation of innate immune cell function by mTOR. Nat Rev Immunol. 15:599–614. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Huang SC, Smith AM, Everts B, Colonna M, Pearce EL, Schilling JD and Pearce EJ: Metabolic reprogramming mediated by the mTORC2-IRF4 signaling axis is essential for macrophage alternative activation. Immunity. 45:817–830. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Brown J, Wang H, Suttles J, Graves DT and Martin M: Mammalian target of rapamycin complex 2 (mTORC2) negatively regulates Toll-like receptor 4-mediated inflammatory response via FoxO1. J Biol Chem. 286:44295–44305. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Covarrubias AJ, Aksoylar HI, Yu J, Snyder NW, Worth AJ, Iyer SS, Wang J, Ben-Sahra I, Byles V, Polynne-Stapornkul T, et al: Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. Elife. 5:pii: e11612. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Sun H, Gong S, Carmody RJ, Hilliard A, Li L, Sun J, Kong L, Xu L, Hilliard B, Hu S, et al: TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell. 133:415–426. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Zhu Y, Tao M, Wu J, Meng Y, Xu C, Tian Y, Zhou X, Xiang J, Zhang H and Xie Y: Adenovirus-directed expression of TIPE2 suppresses gastric cancer growth via induction of apoptosis and inhibition of AKT and ERK1/2 signaling. Cancer Gene Ther. 23:98–106. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Lou Y, Zhang G, Geng M, Zhang W, Cui J and Liu S: TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase. PLoS One. 9:e965082014. View Article : Google Scholar : PubMed/NCBI

15 

Li F, Zhu X, Yang Y, Huang L and Xu J: TIPE2 alleviates systemic lupus erythematosus through regulating macrophage polarization. Cell Physiol Biochem. 38:330–339. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Oho M, Nakano R, Nakayama R, Sakurai W, Miyamoto A, Masuhiro Y and Hanazawa S: TIPE2 (tumor necrosis factor alpha-induced protein 8-like 2) is a novel negative regulator of TAK1 signal. J Biol Chem. 291:22650–22660. 2016. View Article : Google Scholar : PubMed/NCBI

17 

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

18 

Ren J, Chen X and Chen ZJ: IKKβ is an IRF5 kinase that instigates inflammation. Proc Natl Acad Sci USA. 111:17438–17443. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Lopez-Pelaez M, Lamont DJ, Peggie M, Shpiro N, Gray NS and Cohen P: Protein kinase IKKβ-catalyzed phosphorylation of IRF5 at Ser462 induces its dimerization and nuclear translocation in myeloid cells. Proc Natl Acad Sci USA. 111:17432–17437. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Mihaly SR, Morioka S, Ninomiya-Tsuji J and Takaesu G: Activated macrophage survival is coordinated by TAK1 binding proteins. PLoS One. 9:e949822014. View Article : Google Scholar : PubMed/NCBI

21 

Chantranupong L, Scaria SM, Saxton RA, Gygi MP, Shen K, Wyant GA, Wang T, Harper JW, Gygi SP and Sabatini DM: The CASTOR proteins are arginine sensors for the mTORC1 pathway. Cell. 165:153–164. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Sun H, Zhuang G, Chai L, Wang Z, Johnson D, Ma Y and Chen YH: TIPE2 controls innate immunity to RNA by targeting the phosphatidylinositol 3-kinase-Rac pathway. J Immunol. 189:2768–2773. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Wang Z, Fayngerts S, Wang P, Sun H, Johnson DS, Ruan Q, Guo W and Chen YH: TIPE2 protein serves as a negative regulator of phagocytosis and oxidative burst during infection. Proc Natl Acad Sci USA. 109:15413–15418. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Munder M: Arginase: An emerging key player in the mammalian immune system. Br J Pharmacol. 158:638–651. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Nissim I, Luhovyy B, Horyn O, Daikhin Y, Nissim I and Yudkoff M: The role of mitochondrially bound arginase in the regulation of urea synthesis: Studies with [U-15N4]arginine, isolated mitochondria, and perfused rat liver. J Biol Chem. 280:17715–17724. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Comalada M, Yeramian A, Modolell M, Lloberas J and Celada A: Arginine and macrophage activation. Methods Mol Biol. 844:223–235. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Rath M, Müller I, Kropf P, Closs EI and Munder M: Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages. Front Immunol. 5:5322014. View Article : Google Scholar : PubMed/NCBI

28 

McNeill E, Crabtree MJ, Sahgal N, Patel J, Chuaiphichai S, Iqbal AJ, Hale AB, Greaves DR and Channon KM: Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation. Free Radic Biol Med. 79:206–216. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Thomas AC and Mattila JT: ‘Of mice and men’: Arginine metabolism in macrophages. Front Immunol. 5:4792014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jiang Y, Li Q, Zhang Y, Gao Y, Jiang L and Chen Z: TIPE2 governs macrophage polarization via negative regulation of mTORC1. Mol Med Rep 17: 952-960, 2018.
APA
Jiang, Y., Li, Q., Zhang, Y., Gao, Y., Jiang, L., & Chen, Z. (2018). TIPE2 governs macrophage polarization via negative regulation of mTORC1. Molecular Medicine Reports, 17, 952-960. https://doi.org/10.3892/mmr.2017.7991
MLA
Jiang, Y., Li, Q., Zhang, Y., Gao, Y., Jiang, L., Chen, Z."TIPE2 governs macrophage polarization via negative regulation of mTORC1". Molecular Medicine Reports 17.1 (2018): 952-960.
Chicago
Jiang, Y., Li, Q., Zhang, Y., Gao, Y., Jiang, L., Chen, Z."TIPE2 governs macrophage polarization via negative regulation of mTORC1". Molecular Medicine Reports 17, no. 1 (2018): 952-960. https://doi.org/10.3892/mmr.2017.7991
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang Y, Li Q, Zhang Y, Gao Y, Jiang L and Chen Z: TIPE2 governs macrophage polarization via negative regulation of mTORC1. Mol Med Rep 17: 952-960, 2018.
APA
Jiang, Y., Li, Q., Zhang, Y., Gao, Y., Jiang, L., & Chen, Z. (2018). TIPE2 governs macrophage polarization via negative regulation of mTORC1. Molecular Medicine Reports, 17, 952-960. https://doi.org/10.3892/mmr.2017.7991
MLA
Jiang, Y., Li, Q., Zhang, Y., Gao, Y., Jiang, L., Chen, Z."TIPE2 governs macrophage polarization via negative regulation of mTORC1". Molecular Medicine Reports 17.1 (2018): 952-960.
Chicago
Jiang, Y., Li, Q., Zhang, Y., Gao, Y., Jiang, L., Chen, Z."TIPE2 governs macrophage polarization via negative regulation of mTORC1". Molecular Medicine Reports 17, no. 1 (2018): 952-960. https://doi.org/10.3892/mmr.2017.7991
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