Regulation of Multidrug Resistance Protein 1 by Tumor Necrosis Factor α in Cultured Glial Cells: Involvement of Nuclear Factor-κB and c-Jun N-Terminal Kinase Signaling Pathways

HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition

“…Pgp expression was upregulated by IL-1␤ and TNF-␣ but profoundly downregulated by IL-6, with an overall decrease in expression with gp120 treatment or HIV-1 isolates exposure (24,39). In contrast, MRP1 expression was upregulated by TNF-␣ and unaltered by IL-1␤ or IL-6, with an overall increase in expression following gp120 treatment (22). These effects were further confirmed in vivo.…”

“…Statistically significant differences in protein expression between groups (negative versus HIV ϩ naïve, negative versus HIV ϩ on ART, and HIV ϩ naive versus HIV ϩ on ART) were determined using GraphPad Prism software, version 5.01 (Graph Pad Software, San Diego, CA) by applying the nonparametric two-tailed Mann-Whitney test with significance defined by a P value of Ͻ0.05. pha [TNF-␣]) which were found to regulate the expression of Pgp and MRP1 through NF-B and JNK signaling pathways (22,24,39). Pgp expression was upregulated by IL-1␤ and TNF-␣ but profoundly downregulated by IL-6, with an overall decrease in expression with gp120 treatment or HIV-1 isolates exposure (24,39).…”

“…Tissue inflammation and cytokine secretion are known to alter functional expression of drug transporters and CYP enzymes in other disease states (e.g., inflammatory bowel syndrome) (21). Furthermore, we and other investigators have previously reported that the functional expression of drug transporters in brain parenchyma, blood-brain and bloodtestis barriers, and sigmoid colon epithelium is altered by the HIV antigens, viral infection-associated inflammation, and ARVs (22)(23)(24)(25)(26)(27)(28). The main objective of this study was to investigate the impact of HIV-1 infection and suppressive ART on the expression of intestinal drug transporters and metabolic enzymes in the intestinal mucosa of HIV-infected subjects.…”

Resveratrol reverses P-glycoprotein-mediated multidrug resistance of U2OS/ADR cells by suppressing the activation of the NF-κB and p38 MAPK signaling pathways

“…In addition, resveratrol can effectively inhibit NF-κB and MAPK pathways (27)(28)(29). It is widely reported that the NF-κB and MAPK signaling pathways play a major role in the molecular mechanisms of P-gp-mediated multidrug resistance, and overexpression of P-gp is one of the important causes of multidrug resistance of tumor cells (12,13). Therefore, the present study investigated whether resveratrol could significantly reduce the levels of P-gp expression and reverse the drug resistance of U2OS/ADR cells by inhibiting the NF-κB and MAPK signaling pathways.…”

“…It is well known that P-gp expression is closely associated with the nuclear factor (NF)-κB signaling pathway (12), the mitogen-activated protein kinase (MAPK) signaling pathway (13), cylooxygenases-2 (14) and phosphoinositide 3-kinase (15). NF-κB can bind to the NF-κB binding sites in the MDR1 promoter region, which results in the activation of the transcription of the MDR1 gene (16).…”