農藥賽滅寧對於imiquimod 誘發乾癬樣皮膚炎小鼠免疫反應之影響

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Title:	農藥賽滅寧對於imiquimod 誘發乾癬樣皮膚炎小鼠免疫反應之影響 Effects of the pesticide cypermethrin on immune responses in mice with imiquimod-induced psoriasis-like dermatitis
Authors:	王育瑩 WANG, YU-YING
Contributors:	食品安全碩士學位學程侯又禎
Keywords:	賽滅寧;乾癬;嗜中性白血球;調節型T細胞;發炎 cypermethrin;psoriasis;neutrophils;regulatory T cells;inflammation
Date:	2021-07-12
Issue Date:	2022-01-24 17:40:47 (UTC+8)
Abstract:	賽滅寧（cypermethrin, CYP）為廣泛使用的合成除蟲菊精類殺蟲劑，近年研究發現CYP會蓄積在皮膚及毛髮，並且會增加齧齒類動物免疫細胞之氧化壓力和血液中促發炎細胞激素的生成，導致發炎反應增強。乾癬為自體免疫功能失調所引起的慢性皮膚發炎疾病，成因與基因遺傳、環境壓力、外傷感染及藥物有關，而CD4+ T細胞比例失衡為引起乾癬的重要因素。目前研究並不清楚由飲食中暴露的CYP是否會影響皮膚健康，故本研究使用健康以及imiquimod（IMQ）誘發乾癬樣皮膚炎的雄性C57BL/6J小鼠，探討飼料中添加CYP是否會影響免疫細胞而誘發或加劇皮膚發炎的狀況。實驗期間所有小鼠皆給予AIN-93G飼料，而CYP暴露組則於飼料中加入不同濃度的CYP，由低至高分別為17.5、35、70 ppm，共進行28天飲食介入。結果顯示，與正常對照組相比，健康小鼠飲食暴露35 ppm CYP會降低血液中調節型T細胞（regulatory T cell, Treg）比率，並提升背部皮膚趨化因子C-X-C motif chemokine ligand 1 (CXCL1) 以及細胞激素interleukin (IL)-17A的基因表現量。以IMQ誘發乾癬樣皮膚炎會導致皮膚出現紅斑、脫屑以及厚度增加的症狀，血液嗜中性白血球比例、單核球比例和血漿IL-17A濃度會顯著增加，並提升皮膚IL-17A及IL-23的基因表現量。乾癬小鼠經由飲食暴露CYP會降低血液Treg比率以及血漿睪固酮濃度，在脾臟中與Treg相關細胞激素IL-10的基因表現量顯著下降；在耳朵皮膚中的嗜中性白血球、樹突狀細胞以及γδlow T細胞比率顯著增加，而背部皮膚中的CXCL1、C-C motif ligand 6、IL-17A以及Toll like receptor 7基因表現量亦顯著提升。背部皮膚組織切片顯示，乾癬小鼠暴露於35和70 ppm CYP會產生較嚴重的棘皮症。綜合上述，28天飲食暴露CYP會降低健康以及乾癬樣皮膚炎小鼠血液中Treg比率，並增加背部皮膚促發炎因子的基因表現量，而對皮膚健康有負面影響。 Cypermethrin (CYP), a pyrethroid pesticide, is used to control insects worldwide. CYP was found to accumulate in the skin and hair, and recent studies indicated that CYP enhanced oxidative stress of immune cells and production of circulating pro-inflammatory cytokines in rodents, leading to more inflammation. Psoriasis is a chronic autoimmune-mediated inflammatory disease, which is caused by genetic and environmental factors, such as stress, trauma, infection and drugs, and dysregulation of CD4+ T-cell population is considered to be the main pathogenesis of psoriasis. It’s not clear that whether dietary exposure to CYP affects the skin health. This study investigated the effects of dietary exposure to CYP on immune-cell populations and skin inflammatory responses. Both healthy and imiquimod (IMQ)-induced psoriatic C57BL/6J mice were used in this study. Mice were fed with either the AIN-93G diet or the diets containing 17.5, 35 and 70 ppm CYP throughout the 28-day experimental period. The results indicated that, compared to the normal control group, dietary exposure to 35 ppm CYP in healthy mice significantly decreased circulating regulatory T cells (Tregs), and upregulated the gene expressions of C-X-C motif chemokine ligand 1 (CXCL1) and interleukin (IL)-17A. Erythema, scales and thickening of the skin were observed in mice with IMQ-induced psoriasis-like dermatitis. IMQ-induced psoriatic mice had higher percentages of circulating neutrophils, monocyte and plasma concentration of IL-17A, and expression levels of IL-17A and IL-23 genes in the skin. Dietary exposure to CYP in psoriatic mice significantly decreased circulating Treg population and plasma testosterone concentration, and suppressed the gene expression of Treg-related cytokine IL-10 in the spleen. Psoriatic mice with CYP exposure had higher percentages of neutrophils, dendritic cells and γδlow T cells in the ear skin, and higher gene expression levels of CXCL1, C-C motif ligand 6, IL-17A and toll like receptor 7 in the back skin. Besides, dietary exposure to 35 and 70 ppm CYP in psoriatic mice had severe acanthosis in back skin histology. These findings suggest that 28-day dietary exposure to CYP in healthy and psoriatic mice led to Treg suppression in blood and inflammatory genes upregulation in the back skin, which may have unfavorable effects on skin health.
Description:	碩士指導教授：侯又禎委員：陳玉華委員：蔡帛蓉
Data Type:	thesis
Appears in Collections:	[Master Program in Food Safety] Dissertations/Theses

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