An interspecies conserved motif of the mouse immune system-released activating agent (ISRAA) induces proliferative effects on human cells

Taha,Safa; Fathallah,Mohamed Dahmani; Bakhiet,Moiz

doi:10.3892/mmr.2014.2225

July-2014 Volume 10 Issue 1

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July-2014 Volume 10 Issue 1

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Article Open Access

An interspecies conserved motif of the mouse immune system-released activating agent (ISRAA) induces proliferative effects on human cells

Authors:
- Safa Taha
- Mohamed Dahmani Fathallah
- Moiz Bakhiet
View Affiliations / Copyright

Affiliations: Department of Molecular Medicine, Princess Al-Jawhara Center for Genetics and Inherited Diseases, Arabian Gulf University, Manama 26671, Bahrain, Biotechnology Program, College of Graduate Studies, Arabian Gulf University, Manama 26671, Bahrain

Copyright: © Taha et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 75-81
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Published online on: May 8, 2014

https://doi.org/10.3892/mmr.2014.2225
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Abstract

We have recently described an immune system-released activating agent (ISRAA) as a nervous system-induced factor that stimulates immune responses in the mouse spleen. However, the human ISRAA has not yet been identified. In this study, we examined the effects of the mouse ISRAA protein on human peripheral blood mononuclear cells (PBMCs), to observe if the biological activity of this molecule is consistent between the two different species. Mouse ISRAA demonstrated dose-dependent dualistic effects on human cells, as 5 µg exhibited positive apoptosis and 50 pg exhibited significant proliferation (P<0.05). Furthermore, immunosuppressed cells from patients undergoing immunosuppressive therapy demonstrated significant proliferation to 50 pg ISRAA (P<0.05). Studies to compare sequences in different species revealed a preserved motif, exhibiting 72% similarity with the interspecies conserved signal peptide motif of tumor necrosis factor receptor 1 (TNFR1). A mutant ISRAA lacking this motif was produced and tested for its biological effects. The mutant ISRAA demonstrated neither apoptotic nor proliferative effects compared with wild type. Therefore, an interspecies conserved domain of ISRAA constitutes the active site of the molecule, and its effects on immunocompromised cells should be investigated for future therapies in the treatment of immunosuppressive disorders.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

An interspecies conserved motif of the mouse immune system-released activating agent (ISRAA) induces proliferative effects on human cells

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