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

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.

authors

Hayashi T,Mo JH,Gong X,Rossetto C,Jang A,Beck L,Elliott GI,Kufareva I,Abagyan R,Broide DH,Lee J,Raz E

doi

10.1073/pnas.0709261104

subject

Has Abstract

pub_date

2007-11-20 00:00:00

pages

18619-24

issue

47

eissn

0027-8424

issn

1091-6490

pii

0709261104

journal_volume

104

pub_type

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