L-tryptophan-kynurenine pathway metabolite 3-hydroxyanthranilic acid induces apoptosis in macrophage-derived cells under pathophysiological conditions.
Accumulation of L-kynurenine and 3-hydroxyanthranilic acid (3HAA) occurs in the monocyte-derived cells following immune stimulation, and may derive from L-tryptophan following induction of indoleamine-2,3-dioxygenase. In the present study, we evaluate the possibility that 3HAA acts as an endogenous inducer of monocyte/macrophage apoptosis. Supplementation with 200 microM of 3HAA, but not other L-tryptophan metabolites tested, significantly increased the number of apoptotic cells in both THP-1 and U937 cells. Catalase, superoxide dismutase and manganese ions markedly enhanced apoptosis in the presence of 3HAA in these cells. The present results suggest that 3HAA induces the macrophage/monocyte apoptosis under certain conditions, which may be relevant to pathophysiology of inflammatory conditions.
Morita
T
T
Department of Laboratory Medicine, Gifu University School of Medicine, Japan. morita@fmsrsa.fukui-med.ac.jp
Saito
K
K
Takemura
M
M
Maekawa
N
N
Fujigaki
S
S
Fujii
H
H
Wada
H
H
Takeuchi
S
S
Noma
A
A
Seishima
M
M
D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014364:Tryptophan / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D015095:3-Hydroxyanthranilic Acid; D007737:Kynurenine; D014364:Tryptophan