Sd. Savkovic et al., EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption, AM J P-GAST, 281(4), 2001, pp. G890-G898
Citations number
50
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Enteropathogenic Escherichia coli (EPEC) alters many functions of the host
intestinal epithelia. Inflammation is initiated by activation of nuclear fa
ctor (NF)-kappaB, and paracellular permeability is enhanced via a Ca2+- and
myosin light-chain kinase (MLCK)-dependent pathway. The aims of this study
were to identify signaling pathways by which EPEC triggers inflammation an
d to determine whether these pathways parallel or diverge from those that a
lter permeability. EPEC-induced phosphorylation and degradation of the prim
ary inhibitor of NF-kappaB (I kappaB alpha) were tumor necrosis factor (TNF
)-alpha and interleukin (IL)-1 beta independent. In contrast to Salmonella
typhimurium, EPEC-stimulated I kappaB alpha degradation and IL-8 expression
did not require Ca2+. Instead, extracellular signal-regulated kinase (ERK)
-1/2 was significantly and rapidly activated. ERK1/2 inhibitors attenuated
I kappaB alpha degradation and IL-8 expression. Although ERK1/2 can activat
e MLCK, its inhibition had no impact on EPEC disruption of the tight juncti
on barrier. In conclusion, EPEC-induced inflammation 1) is TNF-alpha and IL
-1 beta receptor independent, 2) utilizes pathways differently from S. typh
imurium, 3) requires ERK1/2, and 4) employs signals that are distinct from
those that alter permeability. This is the first time that EPEC-activated s
ignaling cascades have been linked to independent functional consequences.