Acute and subacute oral administration of mycotoxin deoxynivalenol exacerbates the pro-inflammatory and pro-pruritic res
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BIOLOGICS
Acute and subacute oral administration of mycotoxin deoxynivalenol exacerbates the pro‑inflammatory and pro‑pruritic responses in a mouse model of allergic dermatitis Ryota Aihara1 · Toa Ookawara1 · Ai Morimoto1 · Naoki Iwashita1,2 · Yoshiichi Takagi1,3 · Atsushi Miyasaka4 · Masayo Kushiro5 · Shiro Miyake6 · Tomoki Fukuyama1 Received: 1 May 2020 / Accepted: 12 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Deoxynivalenol (DON) contamination in food is a public health concern; however, the effect of DON exposure on immune disorders including allergies remains unclear. The aim of this study is to elucidate the effect of oral exposure to DON on proinflammatory and pro-pruritic responses in a mouse model of allergic dermatitis, which was generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type-2 helper T cells. To evaluate acute exposure to DON, the mice were orally administered vehicle alone, 0.1 mg/kg DON, or 0.3 mg/kg DON 48, 24, and 1 h before the final challenge with TDI. To study subacute exposure, the mice were fed DON-contaminated rodent diet (0.3 ppm) during the experimental period. After the itch behavior and ear-swelling response were monitored, the serum, auricular lymph node, and skin tissue were collected for analyzing immunocyte differentiation, cytokine determination, and histological changes. Acute oral administration of DON significantly enhanced pro-inflammatory responses including ear-swelling response, immunocyte infiltration, and cytokine productions. Histological evaluation supported the occurrence of pro-inflammatory responses. In contrast, acute DON exposure only slightly increased itch behavior. Subacute oral exposure to DON significantly up-regulated the inflammatory responses, but showed almost no effect on pruritic response. In vitro evaluation in dendritic cells and keratinocytes indicated that DON pre-exposure induced a dose-dependent significant increase in cytokine production. Our results imply that both acute and subacute exposures to DON are associated with pro-inflammatory responses in cutaneous allergy. Keywords Deoxynivalenol · Allergic dermatitis · Keratinocytes · Dendritic cells · Balb/c mouse · Th2 cells
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00204-020-02875-3) contains supplementary material, which is available to authorized users. * Tomoki Fukuyama t‑fukuyama@azabu‑u.ac.jp 1
Laboratory of Veterinary Pharmacology, Azabu University, 1‑17‑71, Fuchinobe, Chuo‑ku, Sagamihara‑shi, Kanagawa 252‑5201, Japan
2
Bioalchemis, 3‑28‑61 Honshuku‑cho, Fuchu‑shi, Tokyo 183‑0032, Japan
3
Japan SLC,Inc., 85 Ohara‑cho, Kita‑ku, Hamamatsu‑shi, Shizuoka 433‑8102, Japan
Contamination of mycotoxins in food and feed commodities is a serious problem worldwide; therefore, governments around the globe have strengthened countermeasures against mycotoxins through the development of detection methods and disease-resistant crop variet
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