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
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
- Published online on: May 8, 2014 https://doi.org/10.3892/mmr.2014.2225
-
Pages:
75-81
-
Copyright: © Taha
et al. This is an open access article distributed under the
terms of Creative
Commons Attribution License [CC BY_NC 3.0].
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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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