Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact Dermatitis

Background/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized...

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Main Authors: Yukihiro Yoshimura, Momoka Takahashi
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Allergies
Subjects:
Online Access:https://www.mdpi.com/2313-5786/4/4/17
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author Yukihiro Yoshimura
Momoka Takahashi
author_facet Yukihiro Yoshimura
Momoka Takahashi
author_sort Yukihiro Yoshimura
collection DOAJ
description Background/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized to acetate, exerts anti-inflammatory affects by activating AMP-activated protein kinase (AMPK) and suppressing mast cell degranulation. Here, we aimed to assess the immediate and long-term effects of TA on ACD suppression, focusing on AMPK activation, using a 2,4-dinitrofluorobenzene-induced rodent model. Methods: Various concentrations of TA were topically applied to rats with 2,4-dinitrofluorobenzene-induced dermatitis. Ear thickness was measured, and histological analysis was performed to assess the inflammation, mast cell infiltration, and degranulation in the established models. AMPK activation was analyzed via Western blotting, and TA degradation was assessed via gas chromatography-mass spectrometry. Dorsomorphin (an AMPK inhibitor) was used to evaluate the effects of AMPK on ACD. Results: TA significantly inhibited inflammation and mast cell degranulation in a dose-dependent manner, with 0.25 mmol/L showing the most potent effects. It also activated AMPK activation. Notably, AMPK inhibition reversed the effects of TA. Conclusions: Overall, TA exerted immediate and long-term anti-inflammatory effects via AMPK activation and inhibition of mast cell degranulation, showing potential as a non-steroidal therapeutic for ACD.
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spelling doaj-art-fdf3f37b64fa46c4bbc1c010b6e214d42024-12-27T14:05:22ZengMDPI AGAllergies2313-57862024-12-014425426710.3390/allergies4040017Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact DermatitisYukihiro Yoshimura0Momoka Takahashi1Department of Nutrition, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe City 651-2180, JapanDepartment of Nutrition, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe City 651-2180, JapanBackground/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized to acetate, exerts anti-inflammatory affects by activating AMP-activated protein kinase (AMPK) and suppressing mast cell degranulation. Here, we aimed to assess the immediate and long-term effects of TA on ACD suppression, focusing on AMPK activation, using a 2,4-dinitrofluorobenzene-induced rodent model. Methods: Various concentrations of TA were topically applied to rats with 2,4-dinitrofluorobenzene-induced dermatitis. Ear thickness was measured, and histological analysis was performed to assess the inflammation, mast cell infiltration, and degranulation in the established models. AMPK activation was analyzed via Western blotting, and TA degradation was assessed via gas chromatography-mass spectrometry. Dorsomorphin (an AMPK inhibitor) was used to evaluate the effects of AMPK on ACD. Results: TA significantly inhibited inflammation and mast cell degranulation in a dose-dependent manner, with 0.25 mmol/L showing the most potent effects. It also activated AMPK activation. Notably, AMPK inhibition reversed the effects of TA. Conclusions: Overall, TA exerted immediate and long-term anti-inflammatory effects via AMPK activation and inhibition of mast cell degranulation, showing potential as a non-steroidal therapeutic for ACD.https://www.mdpi.com/2313-5786/4/4/17allergic contact dermatitistriacetinacetateAMPK
spellingShingle Yukihiro Yoshimura
Momoka Takahashi
Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact Dermatitis
Allergies
allergic contact dermatitis
triacetin
acetate
AMPK
title Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact Dermatitis
title_full Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact Dermatitis
title_fullStr Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact Dermatitis
title_full_unstemmed Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact Dermatitis
title_short Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact Dermatitis
title_sort effects of triacetin on ampk activation and immune responses in allergic contact dermatitis
topic allergic contact dermatitis
triacetin
acetate
AMPK
url https://www.mdpi.com/2313-5786/4/4/17
work_keys_str_mv AT yukihiroyoshimura effectsoftriacetinonampkactivationandimmuneresponsesinallergiccontactdermatitis
AT momokatakahashi effectsoftriacetinonampkactivationandimmuneresponsesinallergiccontactdermatitis