探討金針菇免疫調節蛋白FIP-fve對於呼吸道發炎與重塑的影響

Effect of FIP-fve on airway inflammation and remodeling in mouse asthma model

李育慈(Yu-Tzu Lee)

指導教授 ： 呂克桓

中山醫學大學/醫學院/醫學研究所/博士(2018年)

摘要

氣喘是一種非常複雜的氣道發炎病症，通常認為是由輔助型第二型T細胞誘發抗原特異性IgE及eosinophils大量增加所造成的。然而最近研究在一些類固醇頑固型的慢性氣喘病患中不只eosinophils高且neutrophils也高。然而這類病患可能與輔助型Th17細胞所分泌的IL-17為主，導致neutrophils的發炎。先前的研究發現金針菇免疫調節蛋白FIP-fve會誘使細胞傾向Th1進而減緩OVA所誘發食物過敏與塵蟎所誘發的呼吸道過敏。
本研究以BALB/c小鼠建立由OVA誘導的急慢性氣喘動物模式，並利用所收集肺泡沖洗液經Liu’s染色確定其發炎細胞浸潤的狀況。且進一步探討急慢性動物致敏模式的差異與評估金針菇免疫調節蛋白是否能治療此種慢性氣喘。研究中亦檢測FIP-fve對IL-17上下游相關路徑所誘發eosinophils發炎的影響,並確定FIP-fve或類固醇在慢性氣喘中氣道重塑相關的MMPs、膠原蛋白及黏素等相關導致肺纖維化前趨物質的變化。
藉由研究結果顯示，FIP-fve能顯著改善急慢性期的呼吸道發炎，且FIP-fve不僅是對於IL-4、IL-5、IL-13具有抑制作用其對於Th17與Th22也具有一定的調節。FIP-fve可能透過升高IL-22且同時減少IL-17的方式來改善慢性期呼吸道重塑的狀況。
FIP-fve具有抗發炎的效果且能反轉呼吸道重塑的問題，因此FIP-fve在未來可能可以開發作為過敏疾病的一種輔助藥物。

關鍵字

急性呼吸道發炎 ； 慢性呼吸道發炎 ； eosinophils ； neutrophils ； IL-17 ； FIP-fve

並列摘要

Asthma is a heterogeneous inflammatory disorder of the airway. Th2 response is usually contributed to high levels of allergen-specific IgE and eosinophilic airway inflammation. Recently, several findings demonstrated that neutrophils, not eosinophils, are the major inflammatory cells in chronic asthma patients with steroid-resistant.FIP-fve is a fungal immunomodulatory protein (FIP) isolated from the fungus Flammulina velutipes that exhibits anti-inflammatory properties on OVA-induced acute food allergy and HDMs-induced airway inflammation. The proposal will focus on the mechanisms of IL-17 axis and their immune-microenvironment in chronic asthma with corticosteroid-resistant.
The first of the study, we will have established the acute asthma model and chronic asthma model with corticosteroid-resistant with female Balb/c mice. We will evaluate the potential therapeutic role of FIP-fve and corticosteroid in an acute or chronic asthma mouse model characterized by increased neutrophils rather than eosinophils using Liu’s staining and BALF cell counts. Moreover, we will confirm that FIP-fve or corticosteroid effect on MMPs, collagen and mucus secretion for airway remodeling in chronic asthma.
According to our results, FIP-fve could improve airway inflammation not only in acute asthma, but also in chronic. FIP-fve could significantly decrease Th2 cytokines (IL-4, IL-5 and IL-13), and regulated Th17 and Th22. FIP-fve may play a role in decrease IL-17 and increase IL-22. Moreover, FIP-fve could also reversed airway remodeling in chronic asthma model.
FIP-fve had anti-inflammatory effects on OVA-induced airway inflammation and an effect to inhibited Th17 cells to reduced airway remodeling and collagen expression. FIP-fve might be a potential alternative therapy for allergic airway diseases.

並列關鍵字

acute/chronic asthma ； eosinophils ； neutrophils ； IL-17 ； FIP-fve

參考文獻

參考文獻

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