A Novel Role for IκB Kinase (IKK) α and IKKβ in ERK-Dependent Up-Regulation of MUC5AC Mucin Transcription by Streptococcus pneumoniae

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.

<i><b>Bifidobacterium</b></i><b> species lower serum glucose, increase expressions of insulin signaling proteins, and improve adipokine profile in diabetic </b><b>mice </b>

“…Toll-like receptors are related to host immune responses (12). To date, three major MAPK pathways have been identified in mammals: ERK, stress-activated protein kinase/JNK, and p38 (12). Our observation that there were no changes in the levels of JNK and p38 MAP kinase under any of the study conditions, while expression of ERK2 was increased, raises the possibility of probiotics playing a Fig.…”

“…However, serum insulin levels were not detectable by the ELISA method within the 5-week treatment period of this study. Toll-like receptors are related to host immune responses (12). To date, three major MAPK pathways have been identified in mammals: ERK, stress-activated protein kinase/JNK, and p38 (12).…”

Vinpocetine Inhibits Streptococcus pneumoniae–Induced Upregulation of Mucin MUC5AC Expression via Induction of MKP-1 Phosphatase in the Pathogenesis of Otitis Media

“…Clinical OM isolates of S. pneumoniae strain 6B, 19F, 23F, and the wellcharacterized D39 were used in this study (12,19). Bioluminescent ST556 derivative of serotype 19F S. pneumoniae strain (ST556 lux ) was provided by Dr. Jing-Ren Zhang (Center for Immunology and Microbial Disease, Tsinghua University, Beijing, China) and has been described previously (20).…”

“…The luciferase reporter gene construct of MUC5AC was described previously (12,19). The expression plasmids dominant-negative (DN) mutants of ERK1 and ERK2 have been described previously (19).…”

Anti-inflammatory properties of chloroform extracts from GW10-45, a new cultivar derived from Pleurotus ferulae, in RAW264.7 murine macrophages

“…세포에 CG45 (100 μg/ml)를 처리한 후 LPS로 자극시 켜 iNOS와 COX-2의 발현량을 Western blot을 통해 비교 한 결과 Fig. 4 NF-κB 및 IκBα 인산화 억제 확인 NF-κB (nuclear factor-κB)는 염증 반응에 있어서 주요 한 전사인자로 염증성 단백질들과 염증성 사이토카인 등 의 전사를 활성화하는 기능을 한다 (Ha et al, 2007). 세 포 외부에서 LPS와 같은 자극이 주어지면 세포 내로 신 호가 전달되어 NF-κB의 억제 단백질인 IκB (inhibitor of NF-κB)α의 인산화가 일어나고 인산화된 IκBα는 분해되 어 NF-κB의 인산화가 일어난다.…”