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"IFN Expression and Regulation in the Human Cervical Epithelium"

Jennifer Couret
Cell Biology, Neuroscience and Physiology Program
B.S. 2012, William Paterson University, Wayne, NJ

Thesis Advisor: Theresa L. Chang, PhD
Associate Professor
Department of Microbiology, Biochemistry and Molecular Genetics

Monday, December 11, 2017
12:00 PM, ICPH 1st Floor Auditorium


Interferon (IFN) is a type I IFN with distinct gene and protein expression characteristics from other type I IFNs such as IFN/. Unlike IFN/, IFN is not induced by Toll-like receptors or interferon regulatory factors (IRFs) -3, -5, or -7. Rather, IFN is constitutively expressed in the epithelium of mucosal tissues including the female reproductive tract (FRT). IFN gene expression can be modulated by estrogen, seminal plasma, and TNF. While IFN has less potent antiviral responses than IFN, it protects primary macrophages against human immunodeficiency virus and mice against infection by herpes simplex virus-2 and Chlamydia. This work aims to gain a better understanding of gene and protein expression of IFN in the human cervical epithelium of the FRT. We demonstrated the expression and secretion of glycosylated bioactive IFN proteins in a mammalian expression system, the Expi293 cell line but not HEK 293T cells, by using the native signal sequence. Primary human cervical cells endogenously expressed IFN proteins that were localized mainly in the perinuclear space and partially in the Golgi apparatus. Immunostaining analysis of the IFN𝜀 expression in cervical tissues revealed that IFN proteins were present most abundantly in the glandular and luminal cervical epithelium. Some IFN proteins were also detected in the stroma. Finally, the differential effects of mucosal cytokines on IFN, IFN, or IFN gene expression in an endocervical cell line and primary cervical cells were investigated. We found that IFN𝜀 gene expression was induced by TNF and IL-1]. Additionally, TNF⍺ activated the IFN promoter through the NFB signaling pathway. In sum, this study offers a better insight into the biology of IFN𝜀 expression and regulation in the epithelium of the FRT.

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