The Effects of Human Immunodeficiency Virus Infection on the Expression of the Drug Efflux Proteins P-glycoprotein and Breast Cancer Resistance Protein in a Human Intestine Model
Document Type
Article
Publication Title
Journal of Pharmacy and Pharmacology
Abstract
Objectives:
In human immunodeficiency virus (HIV) infection, decreased penetration of antiretroviral drugs is postulated to contribute to HIV persistence within lymphoid-rich regions of the gastrointestinal (GI) tract. However, mechanistic explanations for this phenomenon remain unclear. Specifically, investigations of HIV effects on drug efflux proteins within intestinal models are minimal.
Methods:
Using an in-vitro co-culture model of the GI tract, the effects of HIV infection on drug efflux proteins, P-glycoprotein and breast cancer resistance protein (BCRP) were evaluated. The influence of the HIV-1 protein, Tat, and oxidative stress on P-glycoprotein and BCRP was also evaluated.
Key Findings:
P-glycoprotein expression demonstrated an HIV-induced upregulation in Caco-2 cells over time for cells grown in co-culture with resting lymphocytes. BCRP overall expression increased with HIV exposure in activated primary human lymphocytes co-cultured with Caco-2 cells. Tat treatment resulted in no significant alterations in P-glycoprotein (43% increase), BCRP expression, or oxidative stress.
Conclusions:
HIV exposure within an in-vitro intestinal model resulted in increases in P-glycoprotein and BCRP in a cell-specific manner. Additionally, observed changes were not mediated by Tat. Collectively, these results suggest that alterations in BCRP and P-glycoprotein may contribute, in part, to decreased antiretroviral concentrations within the gut-associated lymphoid tissue of the GI tract in HIV infection.
DOI
10.1111/jphp.12329
Publication Date
2-2015
Keywords
breast cancer resistance protein, HIV, HIV-1 Tat, P-glycoprotein
ISSN
2042-7158
Recommended Citation
Ellis K, Marlin J, Taylor TA, Fitting S, Hauser KF, Rice GD, McRae M. The Effects of Human Immunodeficiency Virus Infection on the Expression of the Drug Efflux Proteins P-glycoprotein and Breast Cancer Resistance Protein in a Human Intestine Model. Journal of Pharmacy and Pharmacology. 2015; 67(2). doi: 10.1111/jphp.12329.