详细记录  
题名:A novel role for IkappaB kinase (IKK) alpha and IKKbeta in ERK-dependent up-regulation of MUC5AC mucin transcription by Streptococcus pneumoniae.
作者:Ha U, Lim JH, Jono H, Koga T, Srivastava A, Malley R, Pages G, Pouyssegur J, Li JD.
来源:J Immunol[IF=6.387]. 2007 Feb 1;178(3):1736-47.
URL :http://www.jimmunol.org/cgi/content/full/178/3/1736
日期:070415
摘要: Unhwan Ha2,*,, Jae Hyang Lim2,*,, Hirofumi Jono*,, Tomoaki Koga*,, Amit Srivastava, Richard Malley, Gilles Pags, Jacques Pouyssgur and Jian-Dong Li3,*,

* Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642; Gonda Department of Cell and Molecular Biology, House Ear Institute, University of Southern California, Los Angeles, CA 90057; Childrens Hospital, Harvard Medical School, Boston, MA 02115; and Institute of Signaling, Developmental Biology and Cancer Research, Nice, France

Abstract

Epithelial cells represent the first line of host innate defense against invading microbes by elaborating a range of molecules involved in pathogen clearance. In particular, epithelial mucins facilitate the mucociliary clearance by physically trapping inhaled microbes. Up-regulation of mucin production thus represents an important host innate defense response against invading microbes. How mucin is induced in upper respiratory Streptococcus pneumoniae infections is unknown. In this study, we show that pneumolysin is required for up-regulation of MUC5AC mucin via TLR4-dependent activation of ERK in human epithelial cells in vitro and in mice in vivo. Interestingly, a "second wave" of ERK activation appears to be important in mediating MUC5AC induction. Moreover, IB kinase (IKK) and IKK are distinctly involved in MUC5AC induction via an ERK1-dependent, but IB-p65- and p100-p52-independent, mechanism, thereby revealing novel roles for IKKs in mediating up-regulation of MUC5AC mucin by S. pneumoniae. 5:

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