Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses

Contact hypersensitivity (CHS) is the most common occupational dermatological disease. Dendritic cells (DCs) mediate the sensitization stage of CHS, while T-cells facilitate the effector mechanisms that drive CHS. Black raspberry (<i>Rubus occidentalis</i>, BRB) and BRB phytochemicals po...

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Main Authors: Kelvin Anderson, Nathan Ryan, Arham Siddiqui, Travis Pero, Greta Volpedo, Jessica L. Cooperstone, Steve Oghumu
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/12/6/1701
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author Kelvin Anderson
Nathan Ryan
Arham Siddiqui
Travis Pero
Greta Volpedo
Jessica L. Cooperstone
Steve Oghumu
author_facet Kelvin Anderson
Nathan Ryan
Arham Siddiqui
Travis Pero
Greta Volpedo
Jessica L. Cooperstone
Steve Oghumu
author_sort Kelvin Anderson
collection DOAJ
description Contact hypersensitivity (CHS) is the most common occupational dermatological disease. Dendritic cells (DCs) mediate the sensitization stage of CHS, while T-cells facilitate the effector mechanisms that drive CHS. Black raspberry (<i>Rubus occidentalis</i>, BRB) and BRB phytochemicals possess immunomodulatory properties, but their dietary effects on CHS are unknown. We examined the effects of diets containing BRB and protocatechuic acid (PCA, a constituent of BRB and an anthocyanin metabolite produced largely by gut microbes), on CHS, using a model induced by 2,4-dinitrofluorobenze (DNFB). Mice were fed control diet or diets supplemented with BRB or PCA. In vitro bone-marrow derived DCs and RAW264.7 macrophages were treated with BRB extract and PCA. Mice fed BRB or PCA supplemented diets displayed decreased DNFB-induced ear swelling, marked by decreased splenic DC accumulation. BRB extract diminished DC maturation associated with reduced <i>Cd80</i> expression and Interleukin (IL)-12 secretion, and PCA reduced IL-12. Dietary supplementation with BRB and PCA induced differential decreases in IL-12-driven CHS mediators, including Interferon (IFN)-γ and IL-17 production by T-cells. BRB extracts and PCA directly attenuated CHS-promoting macrophage activity mediated by nitric oxide and IL-12. Our results demonstrate that BRB and PCA mitigate CHS pathology, providing a rationale for CHS alleviation via dietary supplementation with BRB or BRB derived anthocyanins.
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spelling doaj.art-78762b22f2494725ac588a23b25d5e4a2023-11-20T03:04:10ZengMDPI AGNutrients2072-66432020-06-01126170110.3390/nu12061701Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector ResponsesKelvin Anderson0Nathan Ryan1Arham Siddiqui2Travis Pero3Greta Volpedo4Jessica L. Cooperstone5Steve Oghumu6Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Horticulture and Crop Science, The Ohio State University, Columbus, OH 43210, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USAContact hypersensitivity (CHS) is the most common occupational dermatological disease. Dendritic cells (DCs) mediate the sensitization stage of CHS, while T-cells facilitate the effector mechanisms that drive CHS. Black raspberry (<i>Rubus occidentalis</i>, BRB) and BRB phytochemicals possess immunomodulatory properties, but their dietary effects on CHS are unknown. We examined the effects of diets containing BRB and protocatechuic acid (PCA, a constituent of BRB and an anthocyanin metabolite produced largely by gut microbes), on CHS, using a model induced by 2,4-dinitrofluorobenze (DNFB). Mice were fed control diet or diets supplemented with BRB or PCA. In vitro bone-marrow derived DCs and RAW264.7 macrophages were treated with BRB extract and PCA. Mice fed BRB or PCA supplemented diets displayed decreased DNFB-induced ear swelling, marked by decreased splenic DC accumulation. BRB extract diminished DC maturation associated with reduced <i>Cd80</i> expression and Interleukin (IL)-12 secretion, and PCA reduced IL-12. Dietary supplementation with BRB and PCA induced differential decreases in IL-12-driven CHS mediators, including Interferon (IFN)-γ and IL-17 production by T-cells. BRB extracts and PCA directly attenuated CHS-promoting macrophage activity mediated by nitric oxide and IL-12. Our results demonstrate that BRB and PCA mitigate CHS pathology, providing a rationale for CHS alleviation via dietary supplementation with BRB or BRB derived anthocyanins.https://www.mdpi.com/2072-6643/12/6/1701<i>Rubus occidentalis</i>contact hypersensitivityinflammatoryIFN-γdendritic cells
spellingShingle Kelvin Anderson
Nathan Ryan
Arham Siddiqui
Travis Pero
Greta Volpedo
Jessica L. Cooperstone
Steve Oghumu
Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses
Nutrients
<i>Rubus occidentalis</i>
contact hypersensitivity
inflammatory
IFN-γ
dendritic cells
title Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses
title_full Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses
title_fullStr Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses
title_full_unstemmed Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses
title_short Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses
title_sort black raspberries and protocatechuic acid mitigate dnfb induced contact hypersensitivity by down regulating dendritic cell activation and inhibiting mediators of effector responses
topic <i>Rubus occidentalis</i>
contact hypersensitivity
inflammatory
IFN-γ
dendritic cells
url https://www.mdpi.com/2072-6643/12/6/1701
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