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Interleukin-8 production via protease-activated receptor 2 in human esophageal epithelial cells
Ist Teil von
International journal of molecular medicine, 2007-02, Vol.19 (2), p.335-340
Ort / Verlag
Greece: D.A. Spandidos
Erscheinungsjahr
2007
Quelle
MEDLINE
Beschreibungen/Notizen
Interaction between proteases and protease-activated receptor (PAR) 2 has
been proposed to mediate inflammatory and immune response in the gastrointestinal
tract. Recently, increase in interleukin (IL)-8 in the esophageal mucosa has been
associated with the pathogenesis of esophagitis induced by reflux of gastric acids,
bile acids or trypsin. The aims of the present study were to determine PAR2 expression
in normal human esophageal epithelial cells (HEEC) and to evaluate the mediation
of IL-8 production by trypsin-PAR2 interaction in HEEC. Reverse transcription
polymerase chain reaction (RT-PCR) and Western blot analysis revealed that PAR2
mRNA and protein were constitutively expressed in HEEC without upregulation by
the stimulation with tumor necrosis factor α or trypsin. IL-8 was produced in
a dose-dependent fashion when cells were stimulated with a PAR2 agonist such as
trypsin or SLIGKV-amide. Blocking antibody to PAR2, camostat mesilate (a trypsin
inhibitor), p-38 mitogen-activated protein kinase (MAPK) inhibitors or ERK1/2
inhibitors reduced IL-8 production from trypsin-stimulated HEEC. Mutation of the
NFκB-, AP-1- and NF-IL-6-binding site on the IL-8 gene promoter abrogated the
induction of luciferase activities stimulated with trypsin by 100, 80 and 50%,
respectively. These results indicate that PAR2 activation in HEEC by trypsin induces
NFκB- and AP-1-dependent IL-8 production in association with activation of p38
MAPK and ERK1/2, suggesting that esophageal inflammation may be induced by PAR2
activation via reflux of trypsin.