Interleukin-10 Promotes cell proliferation in Epstein-Barr infected B cells through activation of Ras/ERK and phosphorylation of c-Myc

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Jansen Barrett Smith (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Amy Adamson

Abstract: Epstein-Barr virus is a human herpes virus that in conjunction with Malaria is responsible for endemic Burkitt's lymphoma, a B-cell cancer. The main distinguishing characteristic of Burkitt's lymphoma is a constitutively active c-Myc protein. The transcription factor c-Myc is considered to be a proto-oncogene, which is responsible for cell proliferation and differentiation. The activation of c-Myc leads to the production of cyclin D1 and Cdk4, which promote the G1 to S transition of the cell cycle. The activation of c-Myc is dependent on the Ras/ERK pathway, which can be activated by extracellular signals in the form of cytokines. Interleukin-10 is a cytokine that is produced by Burkitt's lymphoma cells and may act as an autocrine growth factor for the cancer. It may be possible that the Ras/ERK pathway can be activated by interleukin-10 in Epstein-Barr virus infected B-cells. This may lead to the phosphorylation of c-Myc and thus the promotion of the cell cycle and mitotic events in Epstein-Barr infected cells. A further understanding of the role of interleukin-10, the Ras/ERK pathway and c-Myc activation may lead to novel therapeutic interventions for Burkitt's lymphoma pathogenesis in Epstein-Barr virus infected B cells. This study was accomplished by treating Burkitt's lymphoma cells, Epstein-Barr virus infected non-Burkitt's lymphoma cells, and non-infected, non-Burkitt's lymphoma cells with interleukin-10 and assessing the effects of interleukin-10 on the Ras/ERK pathway, c-Myc activation and Cyclin D1 production. Phosphorylation of ERK, total c-Myc and Cylclin D1 levels were significantly increased (p<0.05) in Epstein-Barr virus infected cells, where as IL-10 treatment decreased the viability of B cells lacking an Epstein-Barr infection. Ultimately leading to the conclusion, that IL-10 increases proliferation of Epstein-Barr virus infected B-lymphocytes.

Additional Information

Publication
Thesis
Language: English
Date: 2014
Keywords
Epstein-Barr virus, Burkitt's lymphoma
Subjects
Burkitt's lymphoma $x Research
Epstein-Barr virus $x Research
Interleukin-10 $x Therapeutic use

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