Synergistic induction of MUC5AC mucin by nontypeable Haemophilus influenzae and Streptococcus pneumoniae
Synergistic induction of MUC5AC mucin by nontypeable Haemophilus influenzae and Streptococcus pneumoniae
复制标题
不可分型流感嗜血杆菌和肺炎链球菌协同诱导 MUC5AC 粘蛋白。
DOI：
10.1016/j.bbrc.2007.11.060
复制
发表时间：
2008-01-25
影响因子：
3.1
通讯作者：
Li, Jian-Dong
中科院分区：
文献类型：
--
作者：
Shen, Huahao;Yoshida, Hiroki;Li, Jian-Dong
粘蛋白过量产生是慢性呼吸道疾病（CRD）的一个标志，例如慢性阻塞性肺病和哮喘以及中耳炎。尽管不可分型流感嗜血杆菌 (NTHi) 和肺炎链球菌在这些疾病条件下共存，但人们对 NTHi 和肺炎链球菌如何诱导粘蛋白过量产生知之甚少。在这里，我们表明 NTHi 和肺炎链球菌一起存在时，协同诱导 MUC5AC 粘蛋白转录。 TLR2/4-MyD88-TAK1信号级联传递信号来调节MUC5AC的协同诱导。 MKK3/6-p38 和 ERK MAPK 途径的激活是 MUC5AC 协同诱导所必需的。此外，肺炎链球菌与 NTHi 协同作用，通过 AP-1 依赖性机制诱导 MUC5AC 表达。因此，我们的研究为混合感染中 MUC5AC 的协同诱导提供了直接证据，并为我们理解 CRD 和 OM 中多种微生物感染的分子机制带来了新的见解。 (C) 2007 Elsevier Inc. 保留所有权利。
Mucin overproduction is a hallmark of chronic respiratory diseases (CRD) such as chronic obstructive pulmonary disease and asthma, and otitis media. Despite the fact that nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae are co-existing under these disease conditions, little is known about how NTHi and S. pneumoniae induce mucin overproduction. Here we show that NTHi and S. pneumoniae, when present together, synergistically induce MUC5AC mucin transcription. TLR2/4-MyD88-TAK1 signaling cascade transmits signal to regulate the synergistic induction of MUC5AC. The activation of MKK3/6-p38 and ERK MAPK pathways are required for the synergistic induction of MUC5AC. Moreover, S. pneumoniae synergizes with NTHi to induce MUC5AC expression via AP-1-dependent mechanism. Thus, our studies provide direct evidence for the synergistic induction of MUC5AC in mixed infections and bring novel insights into our understanding of molecular mechanisms underlying polymicrobial infections in CRD and OM. (C) 2007 Elsevier Inc. All rights reserved.