Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone

Pediatric Research
Helen PearsonHitesh C Pandya

Abstract

Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described fo...Continue Reading

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Citations

Jul 31, 2016·Journal of Cellular Physiology·Bharathi AravamudanY S Prakash
Oct 20, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Rodney D BrittY S Prakash
Aug 2, 2017·American Journal of Respiratory Cell and Molecular Biology·Rodney Britt, Y S Prakash
May 7, 2020·Frontiers in Pediatrics·Michael B Anthracopoulos, Mark L Everard

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