We have previously demonstrated that oral epithelia produces human beta defensin-2 and-3 (hBD2, 3), innate immune molecules ordinarily inducible under inflammatory conditions for most epithelia, at higher endogenous levels in oral epithelia. Using 2D-DIGE assessment of human oral epithelial cells from HIV+ and HIV- individuals from vulnerable populations (mainly African Americans), we identified 153 proteins of interest;137 (-90%) were down-regulated and 16 were up-regulated in samples obtained from HIV positive individuals versus control. Interestingly, in terms of their biological functions and significance, protein profiles consistent with cell death (apoptosis) were the most numerous followed by cell proliferation proteins as well as immunological response proteins, suggesting that both cellular and innate immune mechanisms may be altered as a result of HIV infection. Understanding the role that the epithelium plays in HIV infection and inherent differential susceptibility properties of epithelial tissues derived from various anatomic locations is of interest. We propose to (I) compare proteomic profiles of human oral epithelial cells (HOECs), female genital track epithelial cells (FGTECs) and skin-derived epithelial cells (SDECs) from HIV+ and HIV- subjects and to examine protein profiles in these epithelia following in vitro challenge with HIV or HAART therapy;(II) Compare innate and cellular immune response molecules among HOECs, FGTECs and SDECs at baseline and following challenge with HIV and HAART treatment as well as among epithelial cells obtained from wart (oral and vaginal) tissue;(III) Determine if proteomic response from HOECs, FGTECs or SDECs are altered by co-incubation with immune-derived undifferentiated and/or differentiated cells following exposure to human beta defensins. We hypothesize that beta defensins, and other antimicrobial peptides are elevated in tissue undergoing growth and high proliferation rates and that elevated levels of innate immune molecules could result in less viral transmission through the mucosal barrier. Additionally, oral complications of HIV infection may be altered by HIV therapeutics such as HAART or differences in endogenous levels of antimicrobial peptides. By studying protein profiles in the genital epithelia, a site extremely susceptible to HIV trancytosis and infection, and comparing them to oral and skin mucosa, new insights will be gained which could then be translated in the future into promoting protection in vulnerable mucosal barriers.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDE1-JH)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Case Western Reserve University
United States
Zip Code
Dazard, Jean-Eudes; Ishwaran, Hemant; Mehlotra, Rajeev et al. (2018) Ensemble survival tree models to reveal pairwise interactions of variables with time-to-events outcomes in low-dimensional setting. Stat Appl Genet Mol Biol 17:
DasGupta, Twishasri; Nweze, Emeka I; Yue, Hong et al. (2016) Human papillomavirus oncogenic E6 protein regulates human ?-defensin 3 (hBD3) expression via the tumor suppressor protein p53. Oncotarget 7:27430-44
Mehlotra, Rajeev K; Zimmerman, Peter A; Weinberg, Aaron (2016) Defensin gene variation and HIV/AIDS: a comprehensive perspective needed. J Leukoc Biol 99:687-92
Zapata, Wildeman; Aguilar-Jiménez, Wbeimar; Feng, Zhimin et al. (2016) Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV-1. Microbes Infect 18:211-9
Judge, Chelsey J; Reyes-Aviles, Elane; Conry, Sara J et al. (2015) HBD-3 induces NK cell activation, IFN-? secretion and mDC dependent cytolytic function. Cell Immunol 297:61-8
Feng, Zhimin; Jia, Xun; Adams, Mark D et al. (2014) Epithelial innate immune response to Acinetobacter baumannii challenge. Infect Immun 82:4458-65
Chung, Charlotte Y; Alden, Stephanie L; Funderburg, Nicholas T et al. (2014) Progressive proximal-to-distal reduction in expression of the tight junction complex in colonic epithelium of virally-suppressed HIV+ individuals. PLoS Pathog 10:e1004198
Willie, B; Hall, N B; Stein, C M et al. (2014) Association of Toll-like receptor polymorphisms with HIV status in North Americans. Genes Immun 15:569-77
Cheruvu, Vinay K; Igo Jr, Robert P; Jurevic, Richard J et al. (2014) African ancestry influences CCR5 -2459G>A genotype-associated virologic success of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 66:102-7
Mehlotra, R K; Zimmerman, P A; Weinberg, A et al. (2013) Variation in human ?-defensin genes: new insights from a multi-population study. Int J Immunogenet 40:261-9

Showing the most recent 10 out of 29 publications