PMID- 32517233 OWN - NLM STAT- MEDLINE DCOM- 20210301 LR - 20210301 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 12 IP - 6 DP - 2020 Jun 6 TI - Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses. LID - 10.3390/nu12061701 [doi] LID - 1701 AB - 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 (Rubus occidentalis, 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 Cd80 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)-gamma 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. FAU - Anderson, Kelvin AU - Anderson K AD - Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. FAU - Ryan, Nathan AU - Ryan N AD - Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. AD - Division of Anatomy, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. FAU - Siddiqui, Arham AU - Siddiqui A AD - Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. FAU - Pero, Travis AU - Pero T AD - Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. AD - College of Dentistry, The Ohio State University, Columbus, OH 43210, USA. FAU - Volpedo, Greta AU - Volpedo G AUID- ORCID: 0000-0002-1112-7715 AD - Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. AD - Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA. FAU - Cooperstone, Jessica L AU - Cooperstone JL AD - Department of Horticulture and Crop Science, The Ohio State University, Columbus, OH 43210, USA. AD - Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA. FAU - Oghumu, Steve AU - Oghumu S AUID- ORCID: 0000-0001-5177-0652 AD - Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. LA - eng GR - K01 CA207599/CA/NCI NIH HHS/United States GR - K01CA207599/CA/NCI NIH HHS/United States GR - Seed Grant/Foods for Health (FFH) Discovery Theme & Food Innovation Center (FIC)/ PT - Journal Article DEP - 20200606 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (B7-1 Antigen) RN - 0 (Hydroxybenzoates) RN - 0 (Interleukin-17) RN - 0 (Plant Extracts) RN - 187348-17-0 (Interleukin-12) RN - 36R5QJ8L4B (protocatechuic acid) RN - 82115-62-6 (Interferon-gamma) RN - D241E059U6 (Dinitrofluorobenzene) SB - IM MH - Animals MH - B7-1 Antigen/metabolism MH - Dendritic Cells/*immunology MH - Dermatitis, Contact/etiology/*immunology/metabolism/*therapy MH - *Dietary Supplements MH - Dinitrofluorobenzene/*adverse effects MH - Disease Models, Animal MH - Hydroxybenzoates/*pharmacology/*therapeutic use MH - Interferon-gamma/metabolism MH - Interleukin-12/metabolism MH - Interleukin-17/metabolism MH - Mice MH - Mice, Inbred BALB C MH - *Phytotherapy MH - Plant Extracts/*pharmacology/*therapeutic use MH - RAW 264.7 Cells MH - *Rubus MH - T-Lymphocytes/immunology PMC - PMC7352349 OTO - NOTNLM OT - IFN-gamma OT - Rubus occidentalis OT - contact hypersensitivity OT - dendritic cells OT - inflammatory COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/06/11 06:00 MHDA- 2021/03/02 06:00 PMCR- 2020/06/01 CRDT- 2020/06/11 06:00 PHST- 2020/05/24 00:00 [received] PHST- 2020/06/04 00:00 [accepted] PHST- 2020/06/11 06:00 [entrez] PHST- 2020/06/11 06:00 [pubmed] PHST- 2021/03/02 06:00 [medline] PHST- 2020/06/01 00:00 [pmc-release] AID - nu12061701 [pii] AID - nutrients-12-01701 [pii] AID - 10.3390/nu12061701 [doi] PST - epublish SO - Nutrients. 2020 Jun 6;12(6):1701. doi: 10.3390/nu12061701.