Abstract
Benzo[a]pyrene (BaP), a major environmental pollutant, activates aryl hydrocarbon receptor (AHR), induces its cytoplasmic-to-nuclear translocation and upregulates the production of cytochrome P450 1A1 (CYP1A1), a xenobiotic metabolizing enzyme which metabolize BaP. The BaP-AHR-CYP1A1 axis generates reactive oxygen species (ROS) and induces proinflammatory cytokines. Although the anti-inflammatory phytochemical baicalein (BAI) is known to inhibit the BaP-AHR-mediated CYP1A1 expression, its subcellular signaling remains elusive. In this study, normal human epidermal keratinocytes and HaCaT keratinocytes were treated with BAI, BaP, or BAI + BaP, and assessed for the CYP1A1 expression, antioxidative pathways, ROS generation, and proinflammatory cytokine expressions. BAI and BAI-containing herbal medicine Wogon and Oren-gedoku-to could inhibit the BaP-induced CYP1A1 expression. In addition, BAI activated antioxidative system nuclear factor-erythroid 2-related factor-2 (NRF2) and heme oxygenase 1 (HMOX1), leading the reduction of BaP-induced ROS production. The BaP-induced IL1A and IL1B was also downregulated by BAI. BAI inhibited the phosphorylation of Src, a component of AHR cytoplasmic complex, which eventually interfered with the cytoplasmic-to-nuclear translocation of AHR. These results indicate that BAI and BAI-containing herbal drugs may be useful for inhibiting the toxic effects of BaP via dual AHR-CYP1A1-inhibiting and NRF2-HMOX1-activating activities.
Highlights
Environmental pollution is a long-lasting problem for human health
To investigate the effects of BAI on the cytochrome P450 1A1 (CYP1A1) expression in keratinocytes, cells were treated with BAI, BaP or both
Since BaP is known to induce proinflammatory cytokines through aryl hydrocarbon receptor (AHR)-CYP1A1 activation and subsequent reactive oxygen species (ROS) production, we examined whether BAI could prevent the BaP-induced proinflammatory cytokine expression
Summary
Environmental pollution is a long-lasting problem for human health. Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) contaminate the soil, food and air particles, including ambient particulate matter of up to 2.5 μm diameter (PM2.5) [1,2]. PAHs, benzo[a]pyrene (BaP) accounts for 27%–67% of the toxicity of airborne particles [3]. Once drawn into the body, BaP binds to a chemical sensor aryl hydrocarbon receptor (AHR) and is metabolized, and the metabolites trigger the following reactions, which eventually damage the cells [5,6]. AHR is a ligand-activated transcription factor and is abundantly expressed in skin cells including epidermal keratinocytes to sense environmental and endogenous chemicals [7,8,9,10]. In the absence of Antioxidants 2020, 9, 507; doi:10.3390/antiox9060507 www.mdpi.com/journal/antioxidants
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