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• W2809838355 abstract "Smoking aggravates HIV-1 pathogenesis and leads to decreased responses to antiretroviral therapy. In this study, we aim to find a molecular mechanism that would explain smoking-induced HIV-1 replication. Benzo(a)pyrene (BaP), a major carcinogen in cigarette, requires metabolic activation through cytochrome P450s (CYPs) to exert its toxic effects. We hypothesized that CYP-mediated BaP metabolism generates reactive oxygen species (ROS), and the resultant oxidative stress aggravates HIV-1 replication. As expected, we observed ~3 to 4-fold increase in HIV-1 replication in U1 cells and human primary macrophages after chronic BaP exposure. We also observed ~30-fold increase in the expression of CYP1A1 at mRNA level, ~2.5-fold increase in its enzymatic activity as well as elevated ROS and cytotoxicity in U1 cells. The knock-down of the CYP1A1 gene using siRNA and treatment with selective CYP inhibitors and antioxidants significantly reduced HIV-1 replication. Further, we observed a nuclear translocation of NF-κB subunits (p50 and p65) after chronic BaP exposure, which was reduced by treatment with siRNA and antioxidants/CYP inhibitors. Suppression of NF-κB pathway using specific NF-κB inhibitors also significantly reduced HIV-1 replication. Altogether, our results suggest that BaP enhances HIV-1 replication in macrophages by a CYP-mediated oxidative stress pathway followed by the NF-κB pathway." @default.
• W2809838355 created "2018-07-10" @default.
• W2809838355 creator A5029258770 @default.
• W2809838355 creator A5048239951 @default.
• W2809838355 creator A5061920817 @default.
• W2809838355 creator A5068270554 @default.
• W2809838355 date "2018-07-10" @default.
• W2809838355 modified "2023-10-12" @default.
• W2809838355 title "Benzo(a)pyrene in Cigarette Smoke Enhances HIV-1 Replication through NF-κB Activation via CYP-Mediated Oxidative Stress Pathway" @default.
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• W2809838355 doi "https://doi.org/10.1038/s41598-018-28500-z" @default.
• W2809838355 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6039513" @default.
• W2809838355 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29991690" @default.
• W2809838355 hasPublicationYear "2018" @default.
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