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

Abstract:

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION:Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Pearson H,Britt RD Jr,Pabelick CM,Prakash YS,Amrani Y,Pandya HC

doi

10.1038/pr.2015.168

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

650-6

issue

6

eissn

0031-3998

issn

1530-0447

pii

pr2015168

journal_volume

78

pub_type

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