Corticosteroids and β2 Agonists Differentially Regulate Rhinovirus-induced Interleukin-6 via Distinct Cis-acting Elements

Autor: Malcolm Johnson, JJ Haas, Michael R. Edwards, Rey A. Panettieri, Sebastian L. Johnston
Rok vydání: 2007
Předmět:
Rhinovirus
Transcription
Genetic
Phosphodiesterase Inhibitors
Interleukin-1beta
Anti-Inflammatory Agents
Pharmacology
medicine.disease_cause
Biochemistry
Pulmonary Disease
Chronic Obstructive
chemistry.chemical_compound
Adrenal Cortex Hormones
Cyclic AMP
Salmeterol Xinafoate
Fluticasone
Medical And Health Sciences
Forskolin
Chemistry
NF-kappa B
Adrenergic beta-Agonists
Biological Sciences
respiratory system
Salmeterol
Life Sciences & Biomedicine
Rolipram
Glucocorticoid
medicine.drug
Biochemistry & Molecular Biology
medicine.medical_specialty
Bronchi
Response Elements
Internal medicine
medicine
Humans
Albuterol
Molecular Biology
Hormone response element
Science & Technology
Picornaviridae Infections
Interleukin-6
Colforsin
Epithelial Cells
Cell Biology
Asthma
respiratory tract diseases
Androstadienes
Endocrinology
Gene Expression Regulation
Hela Cells
Chemical Sciences
CCAAT-Enhancer-Binding Proteins
Cyclic AMP Response Element
Zdroj: Journal of Biological Chemistry. 282:15366-15375
ISSN: 0021-9258
DOI: 10.1074/jbc.m701325200
Popis: Interleukin-6 (IL-6) is a proinflammatory cytokine up-regulated by rhinovirus infection during acute exacerbations of asthma and chronic obstructive pulmonary disease. The role of IL-6 during exacerbations is unclear; however, it is believed IL-6 could contribute to airway and systemic inflammation. In this study we investigate the effects of common asthma treatments fluticasone propionate and beta(2) agonists salmeterol and salbutamol on IL-6 production in BEAS-2B and primary bronchial epithelial cells. Salmeterol and salbutamol enhanced rhinovirus- and IL-1beta-induced IL-6 production; however, fluticasone treatment caused a reduction of IL-6 protein and mRNA. Combined activity of salmeterol and fluticasone at equimolar concentrations had no effect on rhinovirus or IL-1beta induction of IL-6. The induction of IL-6 by salmeterol was dependent upon the beta(2) receptor and could also be induced by cAMP or cAMP-elevating agents forskolin and rolipram. Using transfection of IL-6 promoter reporter constructs, dominant negative mutants, and electromobility shift assays, it was found that NF-kappaB was the only transcription factor required for rhinovirus induction of IL-6 gene expression. Salmeterol caused an augmentation of rhinovirus-induced promoter activation via a mechanism dependent upon the c/EBP and/or CRE (cyclic AMP response element) cis-acting sites. The suppressive effect of FP was dependent upon distinct glucocorticoid response element sequences proximal to the transcriptional start site within the IL-6 promoter. The data demonstrate that beta(2) agonists can augment IL-6 expression by other stimuli in an additive manner via cyclic AMP and that the negative effect of steroids is mediated by glucocorticoid response elements within the IL-6 promoter.
Databáze: OpenAIRE
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