Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin (Journal of Neuroinflammation)

Background: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by varying degrees of dysfunctional social abilities, as well as learning deficits, and stereotypic behaviors. Many ASD patients have `allergic like` symptoms and respond disproportionally to stress. We had shown that the peptide neurotensin (NT) is increased in the serum of young autistic children and that can stimulate extracellular secretion of mitochondrial (mt) DNA (mtDNA), which was also increasesd in the serum of these children. Methods: Human mast cells were stimulated by corticotropin-releasing hormone (CRH), mt, IgE/anti-IgE for either 24 h for measuring vascular endothelial growth factor (VEGF) release by ELISA or 6 h for qPCR. Results: Here we show that CRH augments IgE/anti-IgE-induced human mast cell release of VEGF and that it also induces the expression of IgE receptor (FcepsilonRI) on mast cells. Moreover, we show that sonicated mt also augment VEGF release, and that this effect is blocked by the natural flavone luteolin. Conclusion: These results indicate that stress and infection-mimicking extracellular mt components augment allergic inflammation that may be involved in the early pathogenesis of ASD. Moreover, luteolin inhibits these processes and may be helpful in the treatment of ASD.