氣喘是種慢性呼吸道發炎疾病，會產生咳嗽、呼吸急促和困難等現象，嚴重時甚至會造成氣管重塑 (airway remodeling)。吸入過敏原或刺激物均可能引發呼吸道過度反應、發炎以及免疫系統中輔助型T細胞活化，進而引發氣喘。其中趨化因子 (chemokine) 則會吸引淋巴球、嗜中性白血球和嗜酸性白血球參與發炎反應。人類支氣管上皮細胞 (bronchial epithelial cell) 是接觸過敏原的第一站，也是主要保護屏障。過去文獻指出在氣喘過程中，氣管上皮細胞可分泌細胞激素和趨化因子調控呼吸道發炎反應。本實驗室利用人類嗜酸性白血球陽離子蛋白 (Eosinophil cationic protein、ECP) 中一段序列可辨識並結合細胞表面硫酸乙醯肝素蛋白聚醣 (heparin sulfate proteoglycans) 區域發展新穎細胞穿透胜肽 (CPPecp)。動物實驗顯示 CPPecp 在體內的主要標的肺支氣管上皮細胞，急性氣喘老鼠模型則顯示 CPPecp 不影響肺功能、細胞聚集及趨化因子表現，但與過敏原共同加入時，CPPecp 能降低輔助型T細胞相關細胞激素和趨化因子，並減緩老鼠氣喘症狀。本研究亦探討在支氣管上皮細胞中 ECP 及 CPPecp 的細胞效應，利用即時定量聚合酶鏈鎖反應 (real-time PCR) 及酵素連結免疫分析 (enzyme-linked immunosorbent assay、ELISA) 發現 ECP 會刺激支氣管上皮細胞中趨化因子的基因及蛋白質表現，CPPecp 則能抑制 ECP 及 Interleukin-4 (IL-4) 引起之特定趨化因子表現。另一方面，西方點墨法分析證明 CPPecp 可抑制支氣管上皮細胞中轉錄活化因子，進而影響趨化因子表現。降低趨化因子表現可減少免疫細胞聚集，進而抑制氣喘發炎現象，因此 CPPecp 具有潛力發展成新穎非類固醇氣喘藥物。

Asthma is a common chronic inflammatory disease characterized by reversible airflow obstruction and airway hyperresponsiveness. Bronchial epithelial cells are the frontline protective barrier against mumerous factors of infectious diseases. The cells also play an essential role in antimicrobial function and release several cytokines and chemokines to modulate lung inflammation. Eosinophil cationic protein (ECP), secreted by activated eosinophils, serves as a biomarker for asthma. Recently, a novel cell penetrating peptide derived from a unique heparin binding motif of ECP (CPPecp) has been identified. Biodistribution of CPPecp in vivo mainly accumulated in bronchus and lung epithelial tissues by intranasal and intravenous injection. In addition, asthmatic animal model using BALB/C mice sensitized and challenged by house dust mite (HDM) was established, and physiological functions including pause enhancement (Penh), differenial cell counts in the absence and presence of CPPecp were analyzed. Administration of CPPecp in asthmatic mice showed significant reduction in airway hyperreactivity and asthma-related chemokine expression, suggesting that CPPecp reduced HDM-induced airway inflammation in vivo. Furthermore, regulatory effects of ECP and CPPecp in bronchial epithelial cells were investigated by real-time PCR and enzyme-linked immunosorbent assay (ELISA). ECP up-regulated gene and protein expression of several chemokines, whereas CPPecp down-regulated the expression levels of specific chemokines induced by ECP and interleukin-4 (IL-4), indicating that CPPecp played an important role in regulating inflammatory response of bronchial epithelial cells. Regulatory roles of CPPecp in specific chemokine pathway was further investigated. Western blotting assay indicated that CPPecp decreased ECP- and IL-4-induced transcription factor activiation. This study demonstrated that ECP up-regulated expression of specific chemokine by activating transcription factor whereas CPPecp attenuated development of allergic airway inflammation and airway hyperresponsiveness both in vitro and in vivo. Hence CPPecp might have a potential to be developed as a novel non-steroidal asthma treatment drug.

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