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

Background: Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by varying degrees of dysfunctional social abilities, learning deficits, and stereotypic behaviors. Many patients with ASDs have 'allergy-like' symptoms and respond disproportionally to stress. We have previously shown that the peptide neurotensin (NT) is increased in the serum of young children with autism and that can stimulate extracellular secretion of mitochondrial (mt) DNA which was also increased in the serum of these children. Methods: Human mast cells were stimulated by corticotropin-releasing hormone (CRH), mitochondrial DNA, IgE/anti-IgE, either for 24 hours to measure vascular endothelial growth factor (VEGF) release by ELISA or for 6 hours or quantitative PCR. Results: CRH augmented IgE/anti-IgE-induced human mast-cell release of VEGF and it also induced the expression of IgE receptor (Fc epsilon RI) on mast cells. Moreover, sonicated mitochondria also augmented VEGF release, and this effect was blocked by the natural flavone luteolin. Conclusion: These results indicate that stress and infection-mimicking extracellular mitochondrial components augment allergic inflammation that may be involved in the early pathogenesis of ASDs. Moreover, luteolin inhibits these processes and may be helpful in the treatment of ASDs.