Papers by Estíbaliz Alegre
Immunology Letters, 2006
Indoleamine 2,3-dioxygenase (IDO) is an enzyme that depletes l-tryptophan, which provokes a decre... more Indoleamine 2,3-dioxygenase (IDO) is an enzyme that depletes l-tryptophan, which provokes a decreased T cell response. This enzyme is expressed in human placenta, and can be also induced in many cell types such as monocytes, where endothelial (eNOS) and inducible (iNOS) nitric oxide synthases are also expressed. Previous studies have shown that nitric oxide (NO) inhibits IDO activity, which could cause a suppression of the biological function of IDO when both enzymes are coexpressed. As NO can exert different effects depending on several factors such as its concentration, we studied the effect of low concentrations of NO in the IDO activity in the U-937 and THP-1 monocytic cell lines. Results demonstrated that NO caused a bimodal effect in IDO function in IFN-gamma-stimulated monocytic cells: while high micromolar concentrations of the NO donors SIN-1 and DETA-NO decreased IDO activity, low micromolar concentrations of these NO donors increased IDO activity. Related to this, the NOS inhibitors L-NMMA and aminoguanidine, and the calmodulin antagonist W7 also decreased IDO activity. The effect of NO in IDO activity was not through cGMP production. Immunoprecipitation analysis showed a nitration of the IDO protein in unstimulated and stimulated U-937 and THP-1 cells. However, in monocyte-derived macrophages, with a higher NO production, aminoguanidine increased IDO activity, but the NOS substrate arginine decreased IDO activity. Considering the role of IDO in suppression, these results suggest a function in tolerance of the NOS enzymes depending on the NO production.
Analytical Biochemistry, 2006
Advances in Clinical Chemistry, 2008
In the past years, it has been shown that kynurenines pathway is a regulator of both the innate a... more In the past years, it has been shown that kynurenines pathway is a regulator of both the innate and the adaptive immune responses. Particularly, the initial enzyme of this pathway, indoleamine 2,3-dioxygenase (IDO), is implicated in maintaining tolerance during pregnancy, and also can be expressed in tumors to avoid the immune attack. In this chapter, we will describe how the kynurenine pathway affects the immune system with important implications both in physiology and in pathology. The incorrect activation or blockade suppressive properties of the kynurenine pathway are also implicated in a number of other diseases such as AIDS or autoimmune diseases.
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Papers by Estíbaliz Alegre