PMID- 16123045
OWN - NLM
STAT- MEDLINE
DCOM- 20060104
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 43
DP  - 2005 Oct 28
TI  - Tumor necrosis factor-alpha triggers mucus production in airway epithelium 
      through an IkappaB kinase beta-dependent mechanism.
PG  - 36510-7
AB  - Excessive mucus production by airway epithelium is a major characteristic of a 
      number of respiratory diseases, including asthma, chronic bronchitis, and cystic 
      fibrosis. However, the signal transduction pathways leading to mucus production 
      are poorly understood. Here we examined the potential role of IkappaB kinase beta 
      (IKKbeta) in mucus synthesis in vitro and in vivo. Tumor necrosis factor-alpha 
      (TNF-alpha) or transforming growth factor-alpha stimulation of human epithelial 
      cells resulted in mucus secretion as measured by MUC5AC mRNA and protein. 
      TNF-alpha stimulation induced IKKbeta-dependent p65 nuclear translocation, mucus 
      synthesis, and production of cytokines from epithelial cells. TNF-alpha, but not 
      transforming growth factor-alpha, induced mucus production dependent on 
      IKKbeta-mediated NF-kappaB activation. In vivo, TNF-alpha induced NF-kappaB as 
      determined by whole mouse body bioluminescence. This activation was localized to 
      the epithelium as revealed by LacZ staining in NF-kappaB-LacZ transgenic mice. 
      TNF-alpha-induced mucus production in vivo could also be inhibited by 
      administration into the epithelium of an IKKbeta dominant negative adenovirus. 
      Taken together, our results demonstrated the important role of IKKbeta in 
      TNF-alpha-mediated mucus production in airway epithelium in vitro and in vivo.
FAU - Lora, Jose M
AU  - Lora JM
AD  - Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
FAU - Zhang, Dong Mei
AU  - Zhang DM
FAU - Liao, Sha Mei
AU  - Liao SM
FAU - Burwell, Timothy
AU  - Burwell T
FAU - King, Anne Marie
AU  - King AM
FAU - Barker, Philip A
AU  - Barker PA
FAU - Singh, Latika
AU  - Singh L
FAU - Keaveney, Marie
AU  - Keaveney M
FAU - Morgenstern, Jay
AU  - Morgenstern J
FAU - Gutierrez-Ramos, Jose Carlos
AU  - Gutierrez-Ramos JC
FAU - Coyle, Anthony J
AU  - Coyle AJ
FAU - Fraser, Christopher C
AU  - Fraser CC
LA  - eng
PT  - Journal Article
DEP - 20050825
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Culture Media)
RN  - 0 (Cytokines)
RN  - 0 (MUC5AC protein, human)
RN  - 0 (Muc5ac protein, mouse)
RN  - 0 (Mucin 5AC)
RN  - 0 (Mucins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Synaptotagmin I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Culture Media/metabolism
MH  - Cystic Fibrosis/metabolism
MH  - Cytokines/metabolism
MH  - Epithelium/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - I-kappa B Kinase/*metabolism
MH  - Immunohistochemistry
MH  - Lac Operon
MH  - Lung/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microscopy, Fluorescence
MH  - Mucin 5AC
MH  - Mucins/metabolism
MH  - Mucus/metabolism
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Synaptotagmin I/metabolism
MH  - Temperature
MH  - Tumor Necrosis Factor-alpha/metabolism/*physiology
MH  - Up-Regulation
MH  - beta-Galactosidase/metabolism
EDAT- 2005/08/27 09:00
MHDA- 2006/01/05 09:00
CRDT- 2005/08/27 09:00
PHST- 2005/08/27 09:00 [pubmed]
PHST- 2006/01/05 09:00 [medline]
PHST- 2005/08/27 09:00 [entrez]
AID - S0021-9258(20)59456-8 [pii]
AID - 10.1074/jbc.M507977200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Oct 28;280(43):36510-7. doi: 10.1074/jbc.M507977200. Epub 2005 
      Aug 25.