歐室塵蟎過敏原 Der P 2 誘導人類肺臟纖維細胞增殖與膠原蛋白過度表現之研究
摘要
Der p 2 (DP2), a Dermatophagoides pteronyssinus group 2 allergen, is well-known to cause airway hypersensitivity and highly associates with induction and progression of asthma. Previous studies have shown that DP2 activates several mitogen-activated protein kinase (MAPK) pathways, which is also known to mediate muscarinic receptor-induced human lung fibroblast proliferation. Airway fibroblast proliferation and the consequent fibrosis is an important pathological characteristic of chronic inflammatory and obstructive airway diseases such as asthma, COPD and Idiopathic pulmonary fibrosis - IPF. However, whether DP2 induces proliferation of airway fibroblast and the underlying mechanisms remain sketchy. The present study demonstrated that DP2 increased expression of type I-collagen, fibronectin and alpha-SMA in both mRNA and protein level. In parallel, kinase activation assay revealed that that DP2 enhanced phosphorylation of PI3K/AKT, MAPKs including mitogen-activated protein kinase kinase kinase 1 (MEKK1), c-Jun N-terminal kinase 1 (JNK1) and p38 MAPK (p38).The levels of nuclear β-catenin were increased after treatment by DP2.β-catenin also contributed to DP2-induced type I-collagen, fibronectin and alpha-smooth muscle actin (alpha-SMA). Further, DP2 treatment induced significant proliferation of human lung fibroblast MRC-5 by using MTT assay.Taken together, our findings indicate that DP2 induces proliferation and collagen overexpression of airway fibroblast MRC-5 which may attribute to activation of MAPK and PI3K/AKT pathway and provide a possible mechanism for allergen-induced airway fibrosis.