Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-γ in normal human T lymphocytes

摘要: The physiological role of the multidrug resistance P-glycoprotein (P- gp), which is expressed by normal human T lymphocytes, still largely unknown. To investigate whether or not P-gp involved in transport cytokines, peripheral blood lymphocytes were stimulated with phytohemagglutinin (PHA) absence presence inhibitors, and concentrations cytokines (interleukin-2 [IL-2], IL- 4, IL-6, interferon-gamma [IFN-gamma]) supernatants these cultures quantitated enzyme-linked immunosorbent assay. inhibitors included verapamil (Ver), tamoxifen (Tmx), specific monoclonal antibody UIC2. Release IL-2 was significantly suppressed at that also effective blocking efflux Rhodamine-123 from lymphocytes. mRNA expression different between PHA control inhibitors. Ver Tmx did interfere T-cell activation as determined CD25 CD69 expression. In a nonhematological model, expressing HCT-8 adenocarcinoma cell line, exogenously added shown to exert an inhibitory effect on mediated efflux. addition, transepithelial electrophysiologically tight polarized monolayers examined. A time-dependent flux across dense monolayers, partially inhibited Ver, observed. We investigated release other produced activated cells (IL- IFN-gamma). IL-4 IFN-gamma Tmx, UIC2; however, IL-6 remained unaffected. These data show transmembrane cells. conclude participates (IL-2, IL-4, IFN-gamma)