Background & Aims: To determine the functional role of immune mediators in
the formation of the intestinal barrier, we have examined the regulation of
claudin expression by interleukin (IL)-17 in human intestinal epithelial c
ells. Methods: Expression of claudins, extracellular signal-related (ERK) m
itogen-activated protein kinases (MAPKs), and activated ERK MAPKs was deter
mined by immunoblotting, Claudin membrane association was assessed by immun
ohistochemistry and claudin messenger RNA expression by Northern blot analy
sis. Intestinal epithelial barrier function was characterized through trans
epithelial electrical resistance and mannitol tracer flux. Results: IL-17 i
nduced the development of a paracellular barrier of T84 cell monolayers. In
hibition of ERK activation with the MEK inhibitor PD98059 blocked IL-17 as
well as basal development of tight junctions in T84 cells. IL-17 induced fo
rmation of tight junctions correlated with up-regulation of claudin-1 and c
laudin-2 gene transcription. Inhibition of MEK reduced the activated and ba
sal expression of claudin-2 messenger RNA and protein expression. Functiona
l MEK was required for the expression and membrane association of claudin-2
but not claudin-1 in T84 cells. Conclusions: MEK activity is required for
claudin-mediated formation of tight junctions. IL-17 is able to regulate th
e intestinal barrier through the ERK MARK pathway.