Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth muscle cells: modulation by glucocorticoids and beta-agonists.

Authors

• Alaina J Ammit
• Aili L Lazaar
• Carla Irani
• Geraldine M O'Neill
• Nancy D Gordon
• Yassine Amrani
• Raymond B Penn
• Reynold A Panettieri

Publication/Presentation Date

4-1-2002

Abstract

Recent studies have demonstrated that tumor necrosis factor (TNF)-alpha stimulates the secretion of interleukin (IL)-6 and regulated on activation, normal T cells expressed and secreted (RANTES) from airway smooth muscle (ASM) cells, with the induction of each molecule being differentially regulated (IL-6 increased, RANTES inhibited) by cyclic adenosine monophosphate (cAMP)-elevating agents. In this study we identify the mechanisms mediating IL-6 and RANTES gene transcription in human ASM cells. We found that TNF-alpha induced IL-6 gene expression in ASM cells via a nuclear factor (NF)-kappaB-dependent pathway, whereas RANTES gene expression was mediated via activation of activator protein (AP)-1 and nuclear factor of activated T cells (NF-AT). TNF-alpha-induced IL-6 secretion was only partially inhibited by dexamethasone, yet TNF-alpha-induced RANTES secretion was abolished. beta-Agonists induced IL-6 secretion from ASM via activation of the CRE region of the IL-6 promoter. beta-Agonists augmented TNF-alpha-induced IL-6 secretion, reflecting an additive effect of NF-kappaB and CRE response elements on IL-6 gene expression. In contrast, beta-agonists inhibited TNF-alpha-induced RANTES secretion via an AP-1-independent pathway. Collectively, these data elucidate transcriptional mechanisms mediating TNF-alpha-induced IL-6 and RANTES secretion from ASM cells, and identify the specific cis- or trans-acting elements that determine the differential effects of glucocorticoids and cAMP-elevating agents on the expression of these genes.

Volume

26

Issue

4

First Page

465

Last Page

474

ISSN

1044-1549

Published In/Presented At

Ammit, A. J., Lazaar, A. L., Irani, C., O'Neill, G. M., Gordon, N. D., Amrani, Y., Penn, R. B., & Panettieri, R. A., Jr (2002). Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth muscle cells: modulation by glucocorticoids and beta-agonists. American journal of respiratory cell and molecular biology, 26(4), 465–474. https://doi.org/10.1165/ajrcmb.26.4.4681

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

11919083

Department(s)

Administration and Leadership

Document Type

Article