Adjuvant effect of short chain triacylglycerol tributyrin on a mouse contact hypersensitivity model. (1st March 2018)

• Record Type: Journal Article
• Authors: Sekiguchi, Kota; Ogawa, Erina; Kurohane, Kohta; Konishi, Hideyuki; Mochizuki, Narumi; Manabe, Kei; Imai, Yasuyuki
• Is Part Of: Toxicology letters. Volume 284(2018)
• Page Start: 56
• Page End: 62
• Publication Date: 2018-03-01
• Subjects: ABTS 2, 2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) -- BSA bovine serum albumin -- CHS contact hypersensitivity -- DAG diacylglycerol -- TAG triacylglycerol -- DBP dibutyl phthalate -- DC dendritic cell -- DMEM Dulbecco's modified Eagle's medium -- FBS fetal bovine serum -- FITC fluorescein isothiocyanate -- HRP Horseradish peroxidase -- IFN-γ interferon-γ -- IL-4 interleukin-4 -- mAb monoclonal antibody -- PE phycoerythrin -- Th2 T helper type 2; Adjuvant -- Contact hypersensitivity -- Triacylglycerol -- Tributyrin -- TRPA1; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.11.036
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Fluorescein isothiocyanate (FITC) is a skin sensitizer that requires T helper type 2. Dicarboxylic acid-short chain alcohol esters enhance skin sensitization to FITC. Tributyrin, a triacyl glycerol (TAG), enhanced skin sensitization to FITC. Tributyrin facilitated dendritic cell trafficking from the skin to lymph nodes. A nociceptive TRPA1 cation channel was activated by tributyrin in vitro . Abstract: Little attention has been paid to chemicals that can enhance hypersensitivity caused by other chemicals. We have demonstrated that phthalate esters with short chain alcohols enhance fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) in a mouse model. Furthermore, phthalate esters with such an enhancing effect were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels, which are expressed on a part of sensory neurons, using a TRPA1-expressing cell line. In this study, we examined these activities of esters comprising glycerol and a short chain fatty acid, i.e. dibutyrin and tributyrin. We carried out chemical synthesis of dibutyrin isomers. Each dibutyrin isomer weakly activated TRPA1 and slightly enhanced skin sensitization to FITC. Unexpectedly, TRPA1 activation and enhancement of FITC-CHS were much more evident in the presence of tributyrin. Mechanistically, tributyrin induced increased dendritic cell trafficking from the skin to draining lymph nodes. Tributyrin enhanced interferon-γ (IFN-γ) production by draining lymph nodes, while its effect on interleukin-4 (IL-4) production was relatively less prominent. These results suggested that tributyrin concomitantly caused TRPA1 activation and an adjuvant effect on FITC-CHS.