标题：Activation of NF-κB by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK–IKKα/β–IκBα and MKK3/6–p38 MAP kinase signaling pathways in epithelial cells
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：15
页码：8774-8779
DOI：10.1073/pnas.151236098
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Nontypeable Hemophilus influenzae (NTHi) is an important human pathogen in both children and adults. In children, it causes otitis media, the most common childhood infection and the leading cause of conductive hearing loss in the United States. In adults, it causes lower respiratory tract infections in the setting of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. The molecular mechanisms underlying the pathogenesis of NTHi-induced infections remain undefined, but they may involve activation of NF-{kappa}B, a transcriptional activator of multiple host defense genes involved in immune and inflammatory responses. Here, we show that NTHi strongly activates NF-{kappa}B in human epithelial cells via two distinct signaling pathways, NF-{kappa}B translocation-dependent and -independent pathways. The NF-{kappa}B translocation-dependent pathway involves activation of NF-{kappa}B inducing kinase (NIK)-IKK/{beta} complex leading to I{kappa}B phosphorylation and degradation, whereas the NF-{kappa}B translocation-independent pathway involves activation of MKK3/6-p38 mitogen-activated protein (MAP) kinase pathway. Bifurcation of NTHi-induced NIK-IKK/{beta}-I{kappa}B and MKK3/6-p38 MAP kinase pathways may occur at transforming growth factor-{beta} activated kinase 1 (TAK1). Furthermore, we show that toll-like receptor 2 (TLR2) is required for NTHi-induced NF-{kappa}B activation. In addition, several key inflammatory mediators including IL-1{beta
