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 μM 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 patho-physiology of inflammatory conditions.
KeywordsU937 Cell Quinolinic Acid Anthranilic Acid Kynurenic Acid Picolinic Acid
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