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Oxidative and inflammatory mediators are upregulated in neutrophils of autistic children: Role of IL-17A receptor signaling

2018; Elsevier BV; Volume: 90; Linguagem: Inglês

10.1016/j.pnpbp.2018.12.002

1878-4216

Ahmed Nadeem, Sheikh F. Ahmad, Sabry M. Attia, Laila Al‐Ayadhi, Saleh A. Bakheet, Naif O. Al‐Harbi,

Calcium signaling and nucleotide metabolism

Autism spectrum disorder (ASD) is characterized by repetitive behaviors, impaired social communication and stereotyped interests, and often associated with dysregulations in innate/adaptive immune cells. IL-17A has been linked with abnormal behavioral patterns observed in autistic children and animal models of autism. However, it is yet to be investigated if IL-17A and its receptors are implicated in regulation of oxidative and inflammatory mediators in neutrophils of ASD patients. Therefore, we pursued to identify the effect of IL-17 receptor (IL-17R), and its inflammatory potential in neutrophils from ASD (n = 45) and typically developing control (TDC; n = 40) subjects. IL-17A, its receptor (IL-17R), associated signaling pathways [nuclear transcription factor nuclear factor-kappa B (NF-κB), IL-6 and oxidative stress parameters such as NADPH oxidase (NOX2), inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), and nitrotyrosine] were determined in the neutrophils from TDC and ASD subjects. Our data show that IL-17A expression, and IL-17R are increased in neutrophils of ASD patients. Further, inflammatory signaling pathways such as such as phospho-NFκB, and ROS generating enzymes, i.e. NOX2/iNOS are increased in neutrophils of ASD patients as compared TDC subjects. Furthermore, activation of IL-17A/IL-17R signaling in neutrophils of ASD subjects leads to upregulation of phospho-NFκB, IL-6 and NOX2/ROS, thus suggesting a compelling role of IL-17A in modulation of inflammation. Our study displays for the first time that IL-17A/IL-17R signaling in neutrophils could play a pivotal role in autism through upregulation of oxidative and inflammatory mediators.