title: 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.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: University of Kansas Medical Center, Kansas City, MO, USA.
authors.forename: Kelstan
authors.initials: K
authors.lastname: Ellis
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Marlin
authors.forename: Tracey A H
authors.initials: TA
authors.lastname: Taylor
authors.forename: Sylvia
authors.initials: S
authors.lastname: Fitting
authors.forename: Kurt F
authors.initials: KF
authors.lastname: Hauser
authors.forename: Greg
authors.initials: G
authors.lastname: Rice
authors.forename: MaryPeace
authors.initials: M
authors.lastname: McRae
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D019380:Anti-HIV Agents / Q000378:metabolism / Q000627:therapeutic use; D001943:Breast Neoplasms; D018938:Caco-2 Cells; D018920:Coculture Techniques; D015696:Gene Products, tat / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000821:virology; D008214:Lymphocytes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D015854:Up-Regulation
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D019380:Anti-HIV Agents; D015696:Gene Products, tat; D009363:Neoplasm Proteins
keywords: HIV; HIV-1 Tat; P-glycoprotein; breast cancer resistance protein