Involvement of apoptosis signal-regulating kinase-1 in house dust miteinduced allergic asthma in mice
Involvement of apoptosis signal-regulating kinase-1 in house dust miteinduced allergic asthma in mice
复制标题
凋亡信号调节激酶1在屋尘螨诱导的小鼠过敏性哮喘中的作用
DOI：
10.1016/j.alit.2017.05.007
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发表时间：
2017
影响因子：
6.8
通讯作者：
S.
中科院分区：
文献类型：
--
作者：
Maruoka;S.;Gon;Y.;Mizumura;K.;Okamoto;S.;Tsuya;K.;Shikano;S.;Soda;K.;Naguro;I.;Ichijo;H. and Hashimoto;S.
Allergic asthma is a complex disease characterized by eosinophilic airway inflammation, mucus hyperproduction, and reversible airway obstruction. 1 The presence of house dust mites (HDM) is a major environmental factor associated with the pathogenesis of allergic asthma. A previous study reported that HDM allergens can be recognized by Toll-like receptor 4 (TLR4) on airway epithelial cells, thereby triggering the production of epithelial cellderived cytokines, such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), which induce the cardinal features of asthma. 2 The HDM allergen Der p2 structurally and functionally mimics myeloid differentiation-2 (MD-2), which is a lipopolysaccharide (LPS)-binding component of the TLR4 signaling complex. 3 Furthermore, we have previously reported that MD-2 is highly expressed in lung vascular endothelial cells and increases in the serum during the amplification process of HDM sensitization in an animal model of asthma. 4 Thus, the TLR4/MD-2 complex might be critical for HDM-induced asthma. However, little is known about the downstream regulators of TLR4, which are involved in HDM-induced allergic asthma.Apoptosis signal-regulating kinase 1 (ASK1) is a conserved mitogen-activated protein 3 kinase that activates both Jnk and p38 mitogen-activated protein kinases and is involved in cytokine-and oxidative stress-induced apoptosis, differentiation, and inflammation. 5 A previous study reported that TLR4 ligand (LPS)-mediated intracellular reactive oxygen species (ROS) activate the ASK1/p38 pathway and induce septic shock. 6 Based on this report, we hypothesized that ASK1 is a downstream molecule of TLR4 involved in the regulation of HDM-induced allergic asthma.
