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Atopic dermatitis-like skin lesions are suppressed in fat-1 transgenic mice through the inhibition of inflammasomes.

ABSTRACT: Previous clinical trials have addressed the beneficial effects of fish oil supplementation on atopic dermatitis. Recently, we reported that fat-1 mice, which can convert n-6 to n-3 polyunsaturated fatty acids (PUFAs), are protected against allergic airway inflammation because their Th2 immune responses are suppressed. Here, we examined the effects of endogenously synthesized n-3 PUFAs on atopic dermatitis, a representative Th2-dominant allergic inflammatory disease. Mouse models of atopic dermatitis-like skin lesions were prepared by epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) or house dust mite (HDM) extract to the ears. DNCB-treated fat-1 mice exhibited markedly reduced epidermal thickening, lower mast cell infiltration, and lower serum IgE and histamine compared with wild-type mice. The draining lymph nodes of fat-1 mice were substantially smaller and contained significantly smaller proportions of activated CD4+ T cells and IL-4-producing Th2 cells than those of wild-type mice. Consistent with these findings, the mRNA levels of Th2 cytokines were significantly decreased in DNCB-sensitized skin lesions of fat-1 mice. Lastly, inflammasome activation, IL-1? production, and pyroptotic cell injury were suppressed in fat-1 mice. Similar results were observed in HDM-challenged fat-1 mice. This study confirms the results of previous clinical studies and suggests fish oil supplementation as a therapeutic strategy for atopic dermatitis-like skin lesions.

SUBMITTER: Jang HY

PROVIDER: S-EPMC6001487 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Atopic dermatitis-like skin lesions are suppressed in fat-1 transgenic mice through the inhibition of inflammasomes.

Jang Hyun-Young HY Koo Jeung-Hyun JH Lee Sang-Myeong SM Park Byung-Hyun BH

Experimental & molecular medicine 20180613 6

Previous clinical trials have addressed the beneficial effects of fish oil supplementation on atopic dermatitis. Recently, we reported that fat-1 mice, which can convert n-6 to n-3 polyunsaturated fatty acids (PUFAs), are protected against allergic airway inflammation because their Th2 immune responses are suppressed. Here, we examined the effects of endogenously synthesized n-3 PUFAs on atopic dermatitis, a representative Th2-dominant allergic inflammatory disease. Mouse models of atopic dermat ...[more]

PMID: 29899324

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Project description:BackgroundAtopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice.MethodsAnimals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate.ResultsOur results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups.ConclusionTaken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

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Atopic dermatitis-like skin lesions are suppressed in fat-1 transgenic mice through the inhibition of inflammasomes.

Publications

Atopic dermatitis-like skin lesions are suppressed in fat-1 transgenic mice through the inhibition of inflammasomes.

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