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Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18619-24. Epub 2007 Nov 14.

3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis.

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  • 1Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0663, USA.

Abstract

3-Hydroxyanthranilic acid (HAA), a compound generated during tryptophan metabolism initiated by indoleamine 2,3-dioxygenase, is known to induce T cell death, but its molecular target is not known. Here we report that HAA inhibits NF-kappaB activation upon T cell antigen receptor engagement by specifically targeting PDK1. Inhibition of NF-kappaB by HAA leads to dysfunction and cell death of activated Th2 cells, which in turn suppresses experimental asthma. Inhibition of NF-kappaB and induction of apoptosis is specific to CD4 T cells because HAA does not inhibit NF-kappaB activation or induce cell death upon Toll-like receptor 4 stimulation in dendritic cells. Thus, HAA is a natural inhibitor that restrains T cell expansion and activation.

PMID:
18003900
[PubMed - indexed for MEDLINE]
PMCID:
PMC2141826
Free PMC Article
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