IDO1 Signaling through GCN2 in a Subpopulation of Gr-1 Cells Shifts the IFNγ/IL6 Balance to Promote Neovascularization.

In addition to immunosuppression, it is generally accepted that myeloid-derived suppressor cells (MDSC) also support tumor angiogenesis. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO1) has been implicated in promoting neovascularization through its positioning as a key regulatory node between the inflammatory cytokines IFNγ and IL6. Here, we report that within the heterogeneous expanse of Gr-1 MDSCs, both IDO1 expression and the ability to elicit neovascularization were associated with a minor subset of autofluorescent, CD11b cells.

Reliable detection of indoleamine 2,3 dioxygenase-1 in murine cells and tissues.

The essential amino acid tryptophan is catabolized by the first and rate-limiting enzyme of the kynurenine pathway, indoleamine 2,3-dioxygenase-1 (IDO1). IDO1 is implicated in several diseases including cancer, chronic infection, autoimmune disorders and neurodegenerative diseases. Antibodies that accurately recognize human IDO1 protein in situ in tissues are available, including clone 10.

Preclinical study of the long-range safety and anti-inflammatory effects of high-dose oral meglumine.

Meglumine is a methylamino derivative of sorbitol that is an approved drug excipient. Recent preclinical studies suggest that administration of high-dose oral meglumine can exert beneficial medicinal effects to treat diabetes, obesity, and fatty liver disease (NAFLD/nonalcoholic steatohepatitis [NASH]). Here we address gaps in knowledge about the pharmacology and toxicology of this substance administered at high concentrations to explore its medicinal potential.

Reduction of the expression of the late-onset Alzheimer's disease (AD) risk-factor does not affect amyloid pathology in an AD mouse model.

Alzheimer's disease (AD) is pathologically characterized by the deposition of the β-amyloid (Aβ) peptide in senile plaques in the brain, leading to neuronal dysfunction and eventual decline in cognitive function. Genome-wide association studies have identified the () gene within the second most significant susceptibility locus for late-onset AD. BIN1 is a member of the amphiphysin family of proteins and has reported roles in the generation of membrane curvature and endocytosis.

RhoB antibody alters retinal vascularization in models of murine retinopathy.

Neovascularization in cancer or retinopathy is driven by pathological changes that foster abnormal sprouting of endothelial cells. Mouse genetic studies indicate that the stress-induced small GTPase RhoB is dispensable for normal physiology but required for pathogenic angiogenesis. In diabetic retinopathy, retinopathy of prematurity (ROP) or age-related wet macular degeneration (AMD), progressive pathologic anatomic changes and ischemia foster neovascularization are characterized by abnormal sprouting of endothelial cells.