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-2017 Volume 15 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-2017 Volume 15 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

Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression

  • Authors:
    • Chun‑Feng Ren
    • Ya‑Xin Zhao
    • Chun‑Feng Hou
    • Luan Luan
    • Guo‑Qing Duan
    • Shu‑Jie Li
    • Jian‑Hong Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Rheumatism, The First People's Hospital of Jining, Jining, Shangdong 272000, P.R. China, Department of Pharmaceutical, The First People's Hospital of Jining, Jining, Shangdong 272000, P.R. China, Department of Joint Surgery, The Affiliated Hospital of Jining Medical College, Jining, Shangdong 272000, P.R. China
  • Pages: 460-466
    |
    Published online on: November 28, 2016
       https://doi.org/10.3892/mmr.2016.5968
  • 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

The present study aimed to investigate the role of the soluble programmed death‑1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry. Expression of sPD‑1 in Treg was detected by western blot analysis. Immunosuppressive activity of CD4+CD25‑ Treg was measured via thiazolyl blue in an MTT assay. ELISA was used to detect interleukin‑10 (IL‑10), transforming growth factor beta (TGF-β), interleukin-4 (IL-4), interferon‑γ (IFN-γ) and nuclear factor of activated T cells (NF‑AT). It was observed that in peripheral blood, CD4+CD25-FOXP3+/CD4+ levels were reduced in the RA group (P<0.001), and sPD‑1 levels were markedly higher (P<0.001), compared with the HC group. Additionally, it was observed that relative sPD‑1 protein expression in the small interfering RNA (siRNA)-sPD-1 treated group was reduced compared with the untreated and scrambled siRNA groups (all P<0.0001). The mean fluorescence intensity of CTLA-4 and Foxp3 decreased markedly upon transfection with siRNA-sPD-1 (P<0.001). Compared with the normal CD4+CD25‑ T group, optical density (OD)540 values, IFN-γ/IL-4 concentration ratio and NF‑AT activity in siRNA untreated and scramble groups reduced significantly (all P<0.001). OD540 value, IFN-γ/IL-4 concentration ratio and NF‑AT activity in the siRNA‑sPD‑1 group were significantly upregulated (all P<0.001). Therefore, sPD-1 may suppress the level of CD4+CD25‑ Tregs in the peripheral blood of RA patients, and may be involved in a variety of immune processes mediated by CD4+CD25‑ Tregs.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Wang CH, Yao H, Chen LN, Jia JF, Wang L, Dai JY, Zheng ZH, Chen ZN and Zhu P: CD147 induces angiogenesis through a vascular endothelial growth factor and hypoxia-inducible transcription factor 1α-mediated pathway in rheumatoid arthritis. Arthritis Rheum. 64:1818–1827. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Scott DL, Wolfe F and Huizinga TW: Rheumatoid arthritis. Lancet. 376:1094–1108. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Kingsley G, Scott IC and Scott DL: Quality of life and the outcome of established rheumatoid arthritis. Best Pract Res Clin Rheumatol. 25:585–606. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Kerola AM, Kauppi MJ, Nieminen T, Rantalaiho V, Kautiainen H, Kerola T, Virta LJ, Pohjolainen T and Puolakka K: Psychiatric and cardiovascular comorbidities as causes of long-term work disability among individuals with recent-onset rheumatoid arthritis. Scand J Rheumatol. 44:87–92. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Greisen SR, Rasmussen TK, Stengaard-Pedersen K, Hetland ML, Hørslev-Petersen K, Hvid M and Deleuran B: Increased soluble programmed death-1 (sPD-1) is associated with disease activity and radiographic progression in early rheumatoid arthritis. Scand J Rheumatol. 43:101–108. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Li S, Liao W, Chen M, Shan S, Song Y, Zhang S, Song H and Yuan Z: Expression of programmed death-1 (PD-1) on CD4+ and CD8+ T cells in rheumatoid arthritis. Inflammation. 37:116–121. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Lin YT, Wang CT, Gershwin ME and Chiang BL: The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis. Autoimmun Rev. 10:482–489. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Coffey G, DeGuzman F, Inagaki M, Pak Y, Delaney SM, Ives D, Betz A, Jia ZJ, Pandey A, Baker D, et al: Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis. J Pharmacol Exp Ther. 340:350–359. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Porter DL, Levine BL, Kalos M, Bagg A and June CH: Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 365:725–733. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ and Rudensky AY: Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 504:451–455. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Haile ST, Dalal SP, Clements V, Tamada K and Ostrand-Rosenberg S: Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression. J Immunol. 191:2829–2836. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Ceeraz S, Hall C, Choy EH, Spencer J and Corrigall VM: Defective CD8+CD28+ regulatory T cell suppressor function in rheumatoid arthritis is restored by tumour necrosis factor inhibitor therapy. Clin Exp Immunol. 174:18–26. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Dai S, Jia R, Zhang X, Fang Q and Huang L: The PD-1/PD-Ls pathway and autoimmune diseases. Cell Immunol. 290:72–79. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Bertsias GK, Nakou M, Choulaki C, Raptopoulou A, Papadimitraki E, Goulielmos G, Kritikos H, Sidiropoulos P, Tzardi M, Kardassis D, et al: Genetic, immunologic, and immunohistochemical analysis of the programmed death 1/programmed death ligand 1 pathway in human systemic lupus erythematosus. Arthritis Rheum. 60:207–218. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Kay J and Upchurch KS: ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology (Oxford). 51:(Suppl 6). vi5–9. 2012.PubMed/NCBI

16 

MPN, . World medical association publishes the revised declaration of Helsinki. Natl Med J India. 27:562014.

17 

Kralj JG, Munson MS and Ross D: Total protein quantitation using the bicinchoninic acid assay and gradient elution moving boundary electrophoresis. Electrophoresis. 35:1887–1892. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Boissier MC, Assier E, Biton J, Denys A, Falgarone G and Bessis N: Regulatory T cells (Treg) in rheumatoid arthritis. Joint Bone Spine. 76:10–14. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Heo YJ, Joo YB, Oh HJ, Park MK, Heo YM, Cho ML, Kwok SK, Ju JH, Park KS, Cho SG, et al: IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients. Immunol Lett. 127:150–156. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, et al: Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 72:917–927. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Pedoeem A, Azoulay-Alfaguter I, Strazza M, Silverman GJ and Mor A: Programmed death-1 pathway in cancer and autoimmunity. Clin Immunol. 153:145–152. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Curran MA, Montalvo W, Yagita H and Allison JP: PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA. 107:4275–4280. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Pen JJ, Keersmaecker BD, Heirman C, Corthals J, Liechtenstein T, Escors D, Thielemans K and Breckpot K: Interference with PD-L1/PD-1 co-stimulation during antigen presentation enhances the multifunctionality of antigen-specific T cells. Gene Ther. 21:262–271. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF and Bluestone JA: Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol. 10:1185–1192. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Shen LS, Wang J, Shen DF, Yuan XL, Dong P, Li MX, Xue J, Zhang FM, Ge HL and Xu D: CD4(+)CD25(+)CD127(low/−) regulatory T cells express Foxp3 and suppress effector T cell proliferation and contribute to gastric cancers progression. Clin Immunol. 131:109–118. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Jiao Z, Wang W, Jia R, Li J, You H, Chen L and Wang Y: Accumulation of FoxP3-expressing CD4+CD25+ T cells with distinct chemokine receptors in synovial fluid of patients with active rheumatoid arthritis. Scand J Rheumatol. 36:428–433. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Rico MC, Rough JJ, Del Carpio-Cano FE, Kunapuli SP and Cadena RA DeLa: The axis of thrombospondin-1, transforming growth factor beta and connective tissue growth factor: An emerging therapeutic target in rheumatoid arthritis. Curr Vasc Pharmacol. 8:338–343. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Checker R, Sandur SK, Sharma D, Patwardhan RS, Jayakumar S, Kohli V, Sethi G, Aggarwal BB and Sainis KB: Potent anti-inflammatory activity of ursolic acid, a triterpenoid antioxidant, is mediated through suppression of NF-κB, AP-1 and NF-AT. PloS One. 7:e313182012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ren CF, Zhao YX, Hou CF, Luan L, Duan GQ, Li SJ and Zhao JH: Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression. Mol Med Rep 15: 460-466, 2017.
APA
Ren, C., Zhao, Y., Hou, C., Luan, L., Duan, G., Li, S., & Zhao, J. (2017). Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression. Molecular Medicine Reports, 15, 460-466. https://doi.org/10.3892/mmr.2016.5968
MLA
Ren, C., Zhao, Y., Hou, C., Luan, L., Duan, G., Li, S., Zhao, J."Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression". Molecular Medicine Reports 15.1 (2017): 460-466.
Chicago
Ren, C., Zhao, Y., Hou, C., Luan, L., Duan, G., Li, S., Zhao, J."Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression". Molecular Medicine Reports 15, no. 1 (2017): 460-466. https://doi.org/10.3892/mmr.2016.5968
Copy and paste a formatted citation
x
Spandidos Publications style
Ren CF, Zhao YX, Hou CF, Luan L, Duan GQ, Li SJ and Zhao JH: Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression. Mol Med Rep 15: 460-466, 2017.
APA
Ren, C., Zhao, Y., Hou, C., Luan, L., Duan, G., Li, S., & Zhao, J. (2017). Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression. Molecular Medicine Reports, 15, 460-466. https://doi.org/10.3892/mmr.2016.5968
MLA
Ren, C., Zhao, Y., Hou, C., Luan, L., Duan, G., Li, S., Zhao, J."Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression". Molecular Medicine Reports 15.1 (2017): 460-466.
Chicago
Ren, C., Zhao, Y., Hou, C., Luan, L., Duan, G., Li, S., Zhao, J."Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression". Molecular Medicine Reports 15, no. 1 (2017): 460-466. https://doi.org/10.3892/mmr.2016.5968
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