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

Bour-Jr Wang, Hui-Wen Chiu, Yong-Lin Lee, Chia-Yi Li, Ying-Jan Wang, Yu-Hsuan Lee

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalJournal of Clinical Medicine
Volume7
Issue number12
DOIs
Publication statusPublished - Nov 27 2018

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Inflammasomes
Allergic Contact Dermatitis
Interleukin-1
Apoptosis
Chromium
Inflammation
Industry
Blueberry Plants
Cutaneous Administration
chromium hexavalent ion
pterostilbene
Skin
Endoplasmic Reticulum Stress
Contact Dermatitis
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Keratinocytes
Epidermis
Protein Kinases
Ear

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Pterostilbene Attenuates Hexavalent Chromium-Induced Allergic Contact Dermatitis by Preventing Cell Apoptosis and Inhibiting IL-1β-Related NLRP3 Inflammasome Activation. / Wang, Bour-Jr; Chiu, Hui-Wen; Lee, Yong-Lin; Li, Chia-Yi; Wang, Ying-Jan; Lee, Yu-Hsuan.

In: Journal of Clinical Medicine, Vol. 7, No. 12, 27.11.2018.

Research output: Contribution to journalArticle

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abstract = "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.",
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