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膳食二十二碳六烯酸与花生四烯酸联合改善了小鼠变应原诱导的皮炎。

Dietary docosahexaenoic acid in combination with arachidonic acid ameliorates allergen-induced dermatitis in mice.

机构信息

Allergy-Center-Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Germany.

出版信息

Pediatr Allergy Immunol. 2011 Aug;22(5):497-504. doi: 10.1111/j.1399-3038.2010.01133.x. Epub 2011 Feb 7.

Abstract

OBJECTIVE

In this study, we investigated the impact of dietary docosahexaenoic (DHA) and arachidonic acid (AA) on development and severity of allergen-induced dermatitis.

STUDY DESIGN

In sensitized mice, skin inflammation was induced by ovalbumin. Mice received either a diet containing 0.015% DHA, 0.029% AA or the combination of both. The severity of dermatitis was evaluated by using a clinical skin score (CSS), followed by immunohistologic and cytokine analysis. To unravel potential mechanisms, interleukin (IL)-4 or tumor necrosis factor α-stimulated keratinocytes from the cell line Kera-308 was cultured with different DHA/AA compositions and analyzed regarding proliferation and cytokine production.

RESULTS

Dietary DHA/AA significantly improved the severity of allergen-induced dermatitis as the CSS was reduced by 36 ± 23% (p=0.005). Furthermore, reduced epidermal KI67 expression, increased number of forkhead box P3(+) cells, and elevated IL-10 expression were determined in skin lesions of dietary-treated mice. Correspondingly, in vitro DHA/AA-treated keratinocytes exhibited increased IL-10 expression and produced less thymic stromal lymphopoietin.

CONCLUSION

Dietary DHA/AA supplementation leads to a significant amelioration of allergen-induced dermatitis. This was accompanied with the presence of increased regulatory T cells and IL-10 expression in lesional skin. Moreover, we identify keratinocytes, which play a crucial role in the regulation of skin inflammation, as important targets of DHA/AA supplementation. Future studies are needed to clarify whether DHA/AA acts directly or whether its biologic active metabolites are responsible for these findings. This may unravel novel therapeutical compounds for allergen-induced dermatitis.

摘要

目的

本研究旨在探讨膳食二十二碳六烯酸(DHA)和花生四烯酸(AA)对过敏原诱导性皮炎的发展和严重程度的影响。

研究设计

在致敏小鼠中,卵白蛋白诱导皮肤炎症。小鼠接受含有 0.015% DHA、0.029% AA 或两者组合的饮食。通过临床皮肤评分(CSS)评估皮炎的严重程度,随后进行免疫组织化学和细胞因子分析。为了揭示潜在的机制,用不同的 DHA/AA 组成培养来自细胞系 Kera-308 的白细胞介素(IL)-4 或肿瘤坏死因子α刺激的角质形成细胞,并分析其增殖和细胞因子产生。

结果

膳食 DHA/AA 显著改善了过敏原诱导性皮炎的严重程度,CSS 降低了 36±23%(p=0.005)。此外,在膳食治疗小鼠的皮肤病变中,还确定了表皮 KI67 表达减少、叉头框 P3(+)细胞数量增加和 IL-10 表达升高。相应地,体外 DHA/AA 处理的角质形成细胞表现出增加的 IL-10 表达和产生较少的胸腺基质淋巴细胞生成素。

结论

膳食 DHA/AA 补充可显著改善过敏原诱导的皮炎。这伴随着病变皮肤中调节性 T 细胞和 IL-10 表达的增加。此外,我们确定角质形成细胞在皮肤炎症的调节中起着至关重要的作用,是 DHA/AA 补充的重要靶标。需要进一步的研究来阐明 DHA/AA 是否直接作用,或者其生物活性代谢物是否对此类发现负责。这可能会揭示治疗过敏原诱导性皮炎的新治疗化合物。

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