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Pterostilbene Attenuates Hexavalent Chromium-Induced Allergic Contact Dermatitis by Preventing Cell Apoptosis and Inhibiting IL-1β-Related NLRP3 Inflammasome Activation

1
Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
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Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
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Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
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Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
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Honors in Neuroscience, Neuroscience and Mental Health Institute, Faculty of Science, University of Alberta, Edmonton, AB TG62R3, Canada
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Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
8
Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2018, 7(12), 489; https://doi.org/10.3390/jcm7120489
Received: 20 October 2018 / Revised: 22 November 2018 / Accepted: 23 November 2018 / Published: 27 November 2018
(This article belongs to the Section Clinical Cytology)
Hexavalent chromium (Cr(VI)) is widely used in many industries but can induce contact dermatitis especially in cement industries. Many cement workers suffer from Cr(VI)-induced allergic contact dermatitis (ACD), and prevention and therapeutic strategies are still lacking. Pterostilbene (PT) is a natural compound predominantly found in blueberries. Studies indicate the potential use of PT as an effective anti-oxidative and anti-inflammatory agent. Herein, we investigated the possible mechanisms involved and whether chromium-induced ACD could be effectively inhibited by treating PT. In our in vivo study, epidermal Cr(VI) administration causes cutaneous inflammation in mice ear skin, and the pro-inflammatory cytokines, TNF-α and IL-1β, were found in the epidermis, presenting the level of increase after Cr(VI) treatment. Meanwhile, the results of our in vitro experiment showed that apoptosis and endoplasmic reticulum (ER) stress were induced after treatment with different concentrations of Cr(VI) in HaCaT cells (human keratinocyte). Cr(VI) also induced TNF-α and IL-1β mRNA expressions, through the activation of the p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein kinase 2 (MK2) pathway. Notably, the severity of the skin reactions in the epicutaneous elicitation test significantly diminished when the mouse was treated with PT. Likewise, PT intervention also ameliorated the inflammation and apoptosis of HaCaT cells in vitro. Furthermore, our current findings demonstrated that the NLRP3 inflammasome could be involved in the Cr(VI)-mediated inflammation and apoptosis of ACD. Thus, interrupting this mechanism with proper nontoxic agents, such as PT, could be a new option to improve occupational chromium toxicity and hypersensitivity. View Full-Text
Keywords: hexavalent chromium; pterostilbene; endoplasmic reticulum stress; inflammatory cytokines; NLRP3 inflammasome; allergic contact dermatitis hexavalent chromium; pterostilbene; endoplasmic reticulum stress; inflammatory cytokines; NLRP3 inflammasome; allergic contact dermatitis
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Wang, B.-J.; Chiu, H.-W.; Lee, Y.-L.; Li, C.-Y.; Wang, Y.-J.; Lee, Y.-H. Pterostilbene Attenuates Hexavalent Chromium-Induced Allergic Contact Dermatitis by Preventing Cell Apoptosis and Inhibiting IL-1β-Related NLRP3 Inflammasome Activation. J. Clin. Med. 2018, 7, 489.

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