TY - JOUR
T1 - A novel role for IκB kinase (IKK) α and IKKβ in ERK-dependent up-regulation of MUC5AC mucin transcription by Streptococcus pneumoniae
AU - Ha, Unhwan
AU - Lim, Jae Hyang
AU - Jono, Hirofumi
AU - Koga, Tomoaki
AU - Srivastava, Amit
AU - Malley, Richard
AU - Pagès, Gilles
AU - Pouysségur, Jacques
AU - Li, Jian Dong
PY - 2007/2/1
Y1 - 2007/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33846518459&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.178.3.1736
DO - 10.4049/jimmunol.178.3.1736
M3 - Article
C2 - 17237423
AN - SCOPUS:33846518459
SN - 0022-1767
VL - 178
SP - 1736
EP - 1747
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -