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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
December-2015 Volume 36 Issue 6

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
December-2015 Volume 36 Issue 6

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

Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions

  • Authors:
    • Sahar Elhannan
    • Safa Taha
    • Noureddine Ben Khalaf
    • Halla Bakheit
    • M. Dahmani Fathallah
    • Moiz Bakhiet
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Medicine, Princess Al‑Jawhara Center for Genetics and Inherited Diseases, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain, Biotechnology Program, College of Graduate Studies, Arabian Gulf University, Manama, Bahrain
  • Pages: 1583-1592
    |
    Published online on: October 15, 2015
       https://doi.org/10.3892/ijmm.2015.2376
  • 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 immune system-released activating agent (ISRAA) is an immune mediator activated as a result of a nerve stimulus initiated by immune challenge. We have previously demonstrated that ISRAA and tumor necrosis factor (TNF) receptor 1 (TNFR1) share an interspecies‑conserved motif (72% homology) that induces the apoptosis and proliferation of human peripheral blood mononuclear cells (hPBMCs) in a dose‑dependent manner. In the present study, cytokine profiles were examined in response to the stimulation of hPBMCs with ISRAA. Furthermore, the signaling pathways induced by ISRAA were mapped. The results revealed high measurable levels of TNF‑α, interleukin (IL)‑6, IL‑8, IL‑10 and interferon (IFN)‑γ, but not IL‑4, IL‑17 (IL-17A) or transforming growth factor (TGF)‑β. The analysis of signaling pathways revealed the activation of extracellular‑regulated protein kinase (ERK)1/2 as a downstream signal in the mitogen‑activated protein kinase (MAPK) pathway during TNF‑α and IL‑6 production and apoptosis, but not during proliferation following stimulation with ISRAA by triggering the Fas-associated protein with death domain (FADD). STAT3 was found to be unphosphorylated in the ISRAA‑stimulated hPBMCs, and STAT3 was ubiquitously expressed in unstimulated cells, suggesting that ISRAA has a protein inhibitor of activated STAT (PIAS)‑like activity, by functioning as a negative regulator of the effects of STAT3 on the Janus kinase (JAK)/STAT pathway. The determination of the nature of cytokine responses together with the signaling pathways of cellular activity induced by ISRAA paves the way for the investigation of a potential target of ISRAA and for the development of novel therapeutic approaches for the treatment of immune-regulated disorders.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

View References

1 

Bakhiet M and Taha S: A novel nervous system-induced factor inducing immune responses in the spleen. Immunol Cell Biol. 86:688–699. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Taha S, Fathallah MD and Bakhiet M: An interspecies conserved motif of the mouse immune system-released activating agent (ISRAA) induces proliferative effects on human cells. Mol Med Rep. 10:75–81. 2014.PubMed/NCBI

3 

Arch RH, Gedrich RW and Thompson CB: Tumor necrosis factor receptor-associated factors (TRAFs) - a family of adapter proteins that regulates life and death. Genes Dev. 12:2821–2830. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Chang F, Steelman LS, Shelton JG, Lee JT, Navolanic PM, Blalock WL, Franklin R and McCubrey JA: Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway (Review). Int J Oncol. 22:469–480. 2003.PubMed/NCBI

5 

Elmore S: Apoptosis: a review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Ibelgaufts H: Cytokines. Cytokines & Cells Online Pathfinder Encyclopedia. Version 31.4. Spring/Summer. 2013 edition.

7 

Pollard TD, Earnshaw WC, Lippincott-Schwartz J and Johnson GT: Cell biology. 2nd edition. Saunders/Elsevier; Philadelphia: 2008

8 

Ubersax JA and Ferrell JE Jr: Mechanisms of specificity in protein phosphorylation. Nat Rev Mol Cell Biol. 8:530–541. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Sallusto F and Lanzavecchia A: Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 179:1109–1118. 1994. View Article : Google Scholar : PubMed/NCBI

10 

Cairo MS, Wagner EL, Fraser J, Cohen G, van de Ven C, Carter SL, Kernan NA and Kurtzberg J: Characterization of banked umbilical cord blood hematopoietic progenitor cells and lymphocyte subsets and correlation with ethnicity, birth weight, sex, and type of delivery: A Cord Blood Transplantation (COBLT) Study report. Transfusion. 45:856–866. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Morgan E, Varro R, Sepulveda H, et al: Cytometric bead array: A multiplexed assay platform with applications in various areas of biology. Clin Immunol. 110:252–266. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI

13 

Leonard M, Ryan MP, Watson AJ, Schramek H and Healy E: Role of MAP kinase pathways in mediating IL-6 production in human primary mesangial and proximal tubular cells. Kidney Int. 56:1366–1377. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Jones SA, Horiuchi S, Topley N, Yamamoto N and Fuller GM: The soluble interleukin 6 receptor: Mechanisms of production and implications in disease. FASEB J. 15:43–58. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Rao MS, Sun Y, Escary JL, Perreau J, Tresser S, Patterson PH, Zigmond RE, Brulet P and Landis SC: Leukemia inhibitory factor mediates an injury response but not a target-directed developmental transmitter switch in sympathetic neurons. Neuron. 11:1175–1185. 1993. View Article : Google Scholar : PubMed/NCBI

16 

Yamamori T, Fukada K, Aebersold R, Korsching S, Fann MJ and Patterson PH: The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 246:1412–1416. 1989. View Article : Google Scholar : PubMed/NCBI

17 

Lo DC: A central role for ciliary neurotrophic factor? Proc Natl Acad Sci USA. 90:2557–2558. 1993. View Article : Google Scholar : PubMed/NCBI

18 

Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G and Schaper F: Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 374:1–20. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Galabova-Kovacs G, Kolbus A, Matzen D, Meissl K, Piazzolla D, Rubiolo C, Steinitz K and Baccarini M: ERK and beyond: insights from B-Raf and Raf-1 conditional knockouts. Cell Cycle. 5:1514–1518. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Kolch W: Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem J. 351(Pt 2): 289–305. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Pagès G, Guérin S, Grall D, Bonino F, Smith A, Anjuere F, Auberger P and Pouysségur J: Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Science. 286:1374–1377. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Pawson T: Regulation and targets of receptor tyrosine kinases. Eur J Cancer. 38(Suppl 5): S3–S10. 2002. View Article : Google Scholar

23 

Rouse J, Cohen P, Trigon S, Morange M, Alonso-Llamazares A, Zamanillo D, Hunt T and Nebreda AR: A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell. 78:1027–1037. 1994. View Article : Google Scholar : PubMed/NCBI

24 

Galabova-Kovacs G, Catalanotti F, Matzen D, Reyes GX, Zezula J, Herbst R, Silva A, Walter I and Baccarini M: Essential role of B-Raf in oligodendrocyte maturation and myelination during postnatal central nervous system development. J Cell Biol. 180:947–955. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Shaul YD and Seger R: The MEK/ERK cascade: From signaling specificity to diverse functions. Biochim Biophys Acta. 1773:1213–1226. 2007. View Article : Google Scholar

26 

Yoon S and Seger R: The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions. Growth Factors. 24:21–44. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001.PubMed/NCBI

28 

Roux PP and Blenis J: ERK and p38 MAPK-activated protein kinases: A family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 68:320–344. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Brunet A, Roux D, Lenormand P, Dowd S, Keyse S and Pouysségur J: Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry. EMBO J. 18:664–674. 1999. View Article : Google Scholar : PubMed/NCBI

30 

Lenormand P, Sardet C, Pagès G, L'Allemain G, Brunet A and Pouysségur J: Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase (p45mapkk) in fibroblasts. J Cell Biol. 122:1079–1088. 1993. View Article : Google Scholar : PubMed/NCBI

31 

Heinrich PC, Behrmann I, Müller-Newen G, Schaper F and Graeve L: Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 334:297–314. 1998. View Article : Google Scholar : PubMed/NCBI

32 

Mertens C, Zhong M, Krishnaraj R, Zou W, Chen X and Darnell JE Jr: Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N-terminal domain. Genes Dev. 20:3372–3381. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Xu X, Sun YL and Hoey T: Cooperative DNA binding and sequence-selective recognition conferred by the STAT amino-terminal domain. Science. 273:794–797. 1996. View Article : Google Scholar : PubMed/NCBI

34 

Bhat NR and Zhang P: Hydrogen peroxide activation of multiple mitogen-activated protein kinases in an oligodendrocyte cell line: Role of extracellular signal-regulated kinase in hydrogen peroxide-induced cell death. J Neurochem. 72:112–119. 1999. View Article : Google Scholar : PubMed/NCBI

35 

Ishikawa Y and Kitamura M: Anti-apoptotic effect of quercetin: Intervention in the JNK- and ERK-mediated apoptotic pathways. Kidney Int. 58:1078–1087. 2000. View Article : Google Scholar : PubMed/NCBI

36 

Kim YK, Kim HJ, Kwon CH, Kim JH, Woo JS, Jung JS and Kim JM: Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells. J Appl Toxicol. 25:374–382. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Jo SK, Cho WY, Sung SA, Kim HK and Won NH: MEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation and apoptosis. Kidney Int. 67:458–466. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Elhannan S, Taha S, Ben Khalaf N, Bakheit H, Fathallah MD and Bakhiet M: Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions. Int J Mol Med 36: 1583-1592, 2015.
APA
Elhannan, S., Taha, S., Ben Khalaf, N., Bakheit, H., Fathallah, M.D., & Bakhiet, M. (2015). Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions. International Journal of Molecular Medicine, 36, 1583-1592. https://doi.org/10.3892/ijmm.2015.2376
MLA
Elhannan, S., Taha, S., Ben Khalaf, N., Bakheit, H., Fathallah, M. D., Bakhiet, M."Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions". International Journal of Molecular Medicine 36.6 (2015): 1583-1592.
Chicago
Elhannan, S., Taha, S., Ben Khalaf, N., Bakheit, H., Fathallah, M. D., Bakhiet, M."Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions". International Journal of Molecular Medicine 36, no. 6 (2015): 1583-1592. https://doi.org/10.3892/ijmm.2015.2376
Copy and paste a formatted citation
x
Spandidos Publications style
Elhannan S, Taha S, Ben Khalaf N, Bakheit H, Fathallah MD and Bakhiet M: Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions. Int J Mol Med 36: 1583-1592, 2015.
APA
Elhannan, S., Taha, S., Ben Khalaf, N., Bakheit, H., Fathallah, M.D., & Bakhiet, M. (2015). Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions. International Journal of Molecular Medicine, 36, 1583-1592. https://doi.org/10.3892/ijmm.2015.2376
MLA
Elhannan, S., Taha, S., Ben Khalaf, N., Bakheit, H., Fathallah, M. D., Bakhiet, M."Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions". International Journal of Molecular Medicine 36.6 (2015): 1583-1592.
Chicago
Elhannan, S., Taha, S., Ben Khalaf, N., Bakheit, H., Fathallah, M. D., Bakhiet, M."Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions". International Journal of Molecular Medicine 36, no. 6 (2015): 1583-1592. https://doi.org/10.3892/ijmm.2015.2376
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