Anti-inflammatory activity of β2-agonists in primary lung epithelial cells is independent of glucocorticoid receptor
(2007) In European Respiratory Journal 30(5). p.848-856- Abstract
In patients with asthma and chronic obstructive pulmonary disease, the addition of long-acting β2-agonists (LABA) to glucocorticosteroids (GCS) results in better control than increasing the dose of GCS alone. In smooth muscle cells and fibroblasts, one apparent underlying mechanism involves the ability of LABAs to activate the glucocorticoid receptor (GR). The present study investigates the effects of formoterol (FORM), salmeterol (SALM) and budesonide (BUD) on GR activation in bronchial epithelial cells via tumour necrosis factor-α-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) release, GR nuclear translocation and GR-regulated reporter gene activity. Both BUD and FORM inhibited GM-CSF release by ≤50%.... (More)
In patients with asthma and chronic obstructive pulmonary disease, the addition of long-acting β2-agonists (LABA) to glucocorticosteroids (GCS) results in better control than increasing the dose of GCS alone. In smooth muscle cells and fibroblasts, one apparent underlying mechanism involves the ability of LABAs to activate the glucocorticoid receptor (GR). The present study investigates the effects of formoterol (FORM), salmeterol (SALM) and budesonide (BUD) on GR activation in bronchial epithelial cells via tumour necrosis factor-α-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) release, GR nuclear translocation and GR-regulated reporter gene activity. Both BUD and FORM inhibited GM-CSF release by ≤50%. The combination of these two drugs, in clinically relevant concentrations, inhibited GM-CSF release by 85% down to unstimulated levels. A similar inhibition was obtained when combining BUD and SALM. The ability of FORM to inhibit GM-CSF synthesis was not altered by small interfering RNA-mediated depletion of GR and FORM nor SALM-induced GR translocation into the cell nucleus. In addition, FORM did not activate GR-regulated reporter gene activity (SALM was not tested), in contrast to the clear effect of BUD. It was concluded that in bronchial epithelial cells, inhibition of granulocyte-macrophage colony-stimulating factor synthesis by formoterol and salmeterol does not act via previously demonstrated glucocorticoid receptor-related mechanisms, suggesting an alternative pathway in these cells. Copyright
(Less)
- author
- Lovén, J. ; Svitacheva, N. LU ; Jerre, A. ; Miller-Larsson, A. and Korn, S. H.
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- keywords
- Anti-inflammatory, Glucocorticoid receptor, Granulocyte-macrophage colony-stimulating factor, Long-acting β-agonists, Small interfering RNA, Western blot
- in
- European Respiratory Journal
- volume
- 30
- issue
- 5
- pages
- 848 - 856
- publisher
- European Respiratory Society
- external identifiers
-
- scopus:38849123625
- pmid:17596271
- ISSN
- 0903-1936
- DOI
- 10.1183/09031936.00129606
- language
- English
- LU publication?
- no
- id
- e7bcbccb-19d3-4215-a7b5-c374347f29d2
- date added to LUP
- 2020-02-25 16:38:53
- date last changed
- 2024-03-04 15:08:29
@article{e7bcbccb-19d3-4215-a7b5-c374347f29d2, abstract = {{<p>In patients with asthma and chronic obstructive pulmonary disease, the addition of long-acting β<sub>2</sub>-agonists (LABA) to glucocorticosteroids (GCS) results in better control than increasing the dose of GCS alone. In smooth muscle cells and fibroblasts, one apparent underlying mechanism involves the ability of LABAs to activate the glucocorticoid receptor (GR). The present study investigates the effects of formoterol (FORM), salmeterol (SALM) and budesonide (BUD) on GR activation in bronchial epithelial cells via tumour necrosis factor-α-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) release, GR nuclear translocation and GR-regulated reporter gene activity. Both BUD and FORM inhibited GM-CSF release by ≤50%. The combination of these two drugs, in clinically relevant concentrations, inhibited GM-CSF release by 85% down to unstimulated levels. A similar inhibition was obtained when combining BUD and SALM. The ability of FORM to inhibit GM-CSF synthesis was not altered by small interfering RNA-mediated depletion of GR and FORM nor SALM-induced GR translocation into the cell nucleus. In addition, FORM did not activate GR-regulated reporter gene activity (SALM was not tested), in contrast to the clear effect of BUD. It was concluded that in bronchial epithelial cells, inhibition of granulocyte-macrophage colony-stimulating factor synthesis by formoterol and salmeterol does not act via previously demonstrated glucocorticoid receptor-related mechanisms, suggesting an alternative pathway in these cells. Copyright</p>}}, author = {{Lovén, J. and Svitacheva, N. and Jerre, A. and Miller-Larsson, A. and Korn, S. H.}}, issn = {{0903-1936}}, keywords = {{Anti-inflammatory; Glucocorticoid receptor; Granulocyte-macrophage colony-stimulating factor; Long-acting β-agonists; Small interfering RNA; Western blot}}, language = {{eng}}, number = {{5}}, pages = {{848--856}}, publisher = {{European Respiratory Society}}, series = {{European Respiratory Journal}}, title = {{Anti-inflammatory activity of β<sub>2</sub>-agonists in primary lung epithelial cells is independent of glucocorticoid receptor}}, url = {{http://dx.doi.org/10.1183/09031936.00129606}}, doi = {{10.1183/09031936.00129606}}, volume = {{30}}, year = {{2007}}, }