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

Abstract：

: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.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Nadeem A,Ahmad SF,Attia SM,Al-Ayadhi LY,Bakheet SA,Al-Harbi NO

doi

10.1016/j.pnpbp.2018.12.002

subject

Has Abstract

pub_date

2019-03-02 00:00:00

pages

204-211

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(18)30770-X

journal_volume

pub_type

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