PMID- 16427093
OWN - NLM
STAT- MEDLINE
DCOM- 20060614
LR  - 20181201
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 78
IP  - 26
DP  - 2006 May 22
TI  - Metalloprotease-dependent amphiregulin release mediates tumor necrosis 
      factor-alpha-induced IL-8 secretion in the human airway epithelial cell line 
      NCI-H292.
PG  - 3051-7
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent multifunctional cytokine that 
      plays a central role in the pathogenesis of many inflammatory diseases. 
      Interleukin-8 (IL-8) is a principle neutrophil chemoattractant and activator in 
      humans. The alveolar macrophage-derived TNF-alpha initiates lung inflammation 
      through its ability to stimulate IL-8 synthesis in airway epithelial cells. Since 
      recent studies demonstrated that the stimulation of epidermal growth factor 
      receptor (EGFR) could induce IL-8 secretion, the involvement of EGFR in 
      TNF-alpha-induced IL-8 secretion in airway epithelium-like NCI-H292 cells was 
      investigated in this study. TNF-alpha and epidermal growth factor (EGF) 
      stimulated IL-8 secretion in a time- and concentration-dependent manner. 
      Inhibition of the EGFR by either an anti-EGFR neutralizing antibody or by its 
      specific inhibitor AG1478 (1 microM) blocked TNF-alpha-induced IL-8 secretion. In 
      addition, TNF-alpha stimulated tyrosine phosphorylation of the EGFR within 5 min 
      after stimulation. Further, TNF-alpha-induced IL-8 secretion was completely 
      inhibited by the neutralizing antibody against amphiregulin (AR), an EGFR ligand, 
      suggesting that TNF-alpha-induced IL-8 secretion was mediated by the AR-EGFR 
      pathway. Furthermore, TNF-alpha stimulated the release of AR in a 
      concentration-dependent manner. Finally, both AR and IL-8 release-induced by 
      TNF-alpha were eliminated by pretreatment with either GM6001, a broad-spectrum 
      inhibitor for metalloprotease, or TAPI-1, relatively selective inhibitor for 
      TNF-alpha converting enzyme (TACE). These findings indicate that 
      metalloprotease-mediated AR shedding and subsequent activation of EGFR play a 
      critical role in TNF-alpha-induced IL-8 secretion from the human airway 
      epithelium-like NCI-H292 cells, and that TACE is one of the most possible 
      candidates for metalloprotease responsible for TNF-alpha-induced AR shedding.
FAU - Chokki, Manabu
AU  - Chokki M
AD  - Bio-medical Evaluation Research Department, Pharmaceutical Discovery Research 
      Laboratories, Teijin Pharma Limited, 4-3-2, Asahigaoka, Hino, Tokyo 191-8512, 
      Japan. m.chiyotsuki@teijin.co.jp
FAU - Mitsuhashi, Hiroaki
AU  - Mitsuhashi H
FAU - Kamimura, Takashi
AU  - Kamimura T
LA  - eng
PT  - Journal Article
DEP - 20060119
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Dipeptides)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 
      (N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 
      2-aminoethylamide)
RN  - 0 (N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan 
      methylamide)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Quinazolines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tyrphostins)
RN  - 170449-18-0 (RTKI cpd)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.- (Metalloproteases)
SB  - IM
MH  - Amphiregulin
MH  - Antibodies, Blocking/pharmacology
MH  - Cell Line
MH  - Dipeptides/pharmacology
MH  - EGF Family of Proteins
MH  - Epithelial Cells/drug effects/*metabolism
MH  - ErbB Receptors/antagonists & inhibitors/metabolism
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Hydroxamic Acids/pharmacology
MH  - Immunoblotting
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Interleukin-8/*biosynthesis
MH  - Kinetics
MH  - Metalloproteases/antagonists & inhibitors/*physiology
MH  - Protease Inhibitors/pharmacology
MH  - Quinazolines
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Tyrphostins/pharmacology
EDAT- 2006/01/24 09:00
MHDA- 2006/06/15 09:00
CRDT- 2006/01/24 09:00
PHST- 2005/09/15 00:00 [received]
PHST- 2005/11/22 00:00 [revised]
PHST- 2005/12/02 00:00 [accepted]
PHST- 2006/01/24 09:00 [pubmed]
PHST- 2006/06/15 09:00 [medline]
PHST- 2006/01/24 09:00 [entrez]
AID - S0024-3205(05)01264-6 [pii]
AID - 10.1016/j.lfs.2005.12.023 [doi]
PST - ppublish
SO  - Life Sci. 2006 May 22;78(26):3051-7. doi: 10.1016/j.lfs.2005.12.023. Epub 2006 
      Jan 19.