Th1 Cytokines, TNF α and IFNγ, Promote Corticosteroid Resistance in Developing Human Airway Smooth Muscle.

Th1 Cytokines, TNFα and IFNγ, Promote Corticosteroid Resistance in Developing Human Airway Smooth Muscle. Am J Physiol Lung Cell Mol Physiol. 2018 Oct 18;: Authors: Britt RD, Thompson MA, Sasse SK, Pabelick CM, Gerber AN, Prakash YS Abstract Corticosteroids are commonly used to manage wheezing and asthma in pediatric populations. Although corticosteroids are effective in alleviating airway diseases, some children with more moderate-severe asthma phenotypes show corticosteroid (CS) resistance and exhibit significant airflow obstruction, persistent inflammation, and more frequent exacerbations. Previous studies have demonstrated that Th1 cytokines, such as TNFα and IFNγ, promote corticosteroid resistance in adult human airway smooth muscle (ASM). In the present study, using a human fetal ASM cell model, we tested the hypothesis that TNFα/IFNγ induces CS resistance. In contrast to TNFα or IFNγ alone, the combination of TNFα/IFNγ blunted the ability of fluticasone propionate (FP) to reduce expression of the chemokines, CCL5 and CXCL10, despite expression of key anti-inflammatory glucocorticoid receptor target genes being largely unaffected by TNFα/IFNγ. Expression of the NFκB subunit, p65, and phosphorylation of Stat1 were elevated in cells treated with TNFα/IFNγ, an effect that remained in the presence of FP. siRNA knockdown studies demonstrated effects of TNFα/IFNγ on increased p65 are mediated by Stat1, a transcriptio...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research