A novel role for IκB kinase (IKK) α and IKKβ in ERK-dependent up-regulation of MUC5AC mucin transcription by Streptococcus pneumoniae

Unhwan Ha, Jae Hyang Lim, Hirofumi Jono, Tomoaki Koga, Amit Srivastava, Richard Malley, Gilles Pagès, Jacques Pouysségur, Jian Dong Li

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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, IκB kinase (IKK) α and IKKβ are distinctly involved in MUC5AC induction via an ERK1-dependent, but IκBα-p65- and p100-p52-independent, mechanism, thereby revealing novel roles for IKKs in mediating up-regulation of MUC5AC mucin by S. pneumoniae.

Original languageEnglish
Pages (from-to)1736-1747
Number of pages12
JournalJournal of Immunology
Volume178
Issue number3
DOIs
StatePublished - 1 Feb 2007

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