Effect of Th17 Cytokines and Corticosteroids on Pediatric Airway Smooth Muscle Proliferation and Migration
Year: 2021
Type: conference-abstract
Abstract: Rationale: Asthma is a chronic inflammation of the lung airways characterized by wheezing and airflow obstruction and adversely affects neonatal and pediatric populations. Airway smooth muscle (ASM) plays a pivotal role in asthma by contributing to airway inflammation, remodeling, and hyperresponsiveness. In addition to Th2 inflammation, increased Th17 inflammation has been observed in severe asthmatic patients who respond poorly to corticosteroid treatment. Studies show that Th17 cytokines, most notably IL-17A and IL-17F, promotes inflammation, hypercontractility, and remodeling in ASM, however their effects on pediatric ASM remains undefined. In the present study, we examined the effect of Th17 cytokines, IL-17A and IL-17F, and corticosteroids on ASM proliferation and migration. Methods: Human pediatric ASM were isolated from donor lungs or trachea of patients undergoing tracheal reconstruction surgery (1-21 years old, approved by NCH IRB). Cultured ASM were treated with vehicle (0.01% DMSO), 1-100 nM fluticasone propionate (FP), 1-100 ng/mL IL-17A, 1-100 ng/mL IL-17F, or 2 ng/mL TGF for 24-72 h. Proliferation was measured by Cyquant 72 h post treatment. Migration was analyzed by scratch wound healing assay. Cells were harvested to measure mRNA levels of pro-migratory chemokines genes by qRT-PCR. Results: ASM treated with 100 ng/mL IL-17A, but not 1 or 10 ng/mL, had increased proliferation. Treatment with 10 ng/mL IL-17A increased wound closure after 36-40 h, which was comparable to the positive control, TGF. Conversely, IL-17F was not found to induce proliferation, while it did increase wound closure. Treatment with 10 ng/mL IL-17A increased expression of ASM migratory chemokines CXCL1, CXCL2, and CXCL3 mRNA. Meanwhile, FP reduced IL-17A-induced proliferation and chemokine mRNA expression. Conclusions: Our novel data shows that IL-17A induces proliferation, migration, and expression of chemokines that have shown to mediate ASM migration. The effects of IL-17A were reduced by treatment with corticosteroids, suggesting that the effects of IL-17A alone are corticosteroid sensitive. Given the asthmatic symptoms in pediatric asthma, it will be important to understand how IL-17A and IL-17F promotes airway thickening and hypercontractility in children with asthma. Studies are supported by the National Institutes of Health R00 HL131682-05 (Britt and Jackson).
Authors: D. Jackson, B.W. Lewis, J. Walum, R.D. Britt
Institution: Nationwide Children's Hospital
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4256135997