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Prokaryotic Regulation of Epithelial Responses by Inhibition of IB- Ubiquitination
Andrew S. Neish,*Andrew T. Gewirtz,Hui Zeng,Andrew N. Young,Michael E. Hobert,Vinit Karmali,Anjali S. Rao,James L. Madara
Epithelia of the vertebrate intestinal tract
characteristically maintain an inflammatory hyporesponsiveness toward
the lumenalprokaryotic microflora. We report the identification of
entericorganisms (nonvirulent Salmonella strains) whose
direct interactionwith model human epithelia attenuate synthesis of
inflammatoryeffector molecules elicited by diverse proinflammatory
stimuli.This immunosuppressive effect involves inhibition of the
inhibitorB/nuclear factor B (IB/NF-B) pathway by blockade
of IB-degradation, which prevents subsequent nuclear
translocation ofactive NF-B dimer. Although
phosphorylation of IB- occurs,subsequent
polyubiquitination necessary for regulated IB- degradationis
completely abrogated. These data suggest that prokaryotic determinantscould be responsible for the unique tolerance of the gastrointestinalmucosa to proinflammatory stimuli.
Epithelial Pathobiology Unit, Department of Pathology and
Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
30322, USA.
*
To whom correspondence should be addressed. E-mail:
aneish{at}emory.edu
Salmonella regulates polyubiquitination and surface expression of MHC class II antigens.
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