Inhibition of chemokine production from human airway smooth muscle cells by fluticasone, budesonide and beclomethasone.
Human airway smooth muscle cells (HASMC) contribute to the process of airway wall remodelling in asthma by virtue of their secretory functions. This study was performed to investigate the effectiveness of the commonly used steroids beclomethasone, budesonide and fluticasone in downregulating HASMC production of RANTES and IL-8. HASMC (n=5) were cultured from dissected bronchi using collagenase digestion. Confluent HASMC were exposed to TNFalpha and IL-1beta (10 ng/ml) for 24 h. All stimulations were set with and without pre-treatment with beclomethasone, budesonide or fluticasone for 2 h at concentrations of 10(-9)-10(-6)M. IL-8 and RANTES mRNA expression was assessed by RT-PCR and protein secretion was determined by ELISA. Pre-treatment with beclomethasone, budesonide or fluticasone reduced TNFalpha- and IL-1beta-stimulated IL-8 and RANTES release from HASMC in a dose dependent manner. However, beclomethasone was 22-28% less effective than fluticasone and budesonide in inhibiting chemokine production. TNFalpha- and IL-1beta-induced RANTES and IL-8 expression was reduced on the transcriptional level by pre-treatment with fluticasone and budesonide. The results suggest that the topical steroids fluticasone, budesonide and to a lesser extent beclomethasone may have beneficial effects on airway inflammation in asthma by reducing RANTES and IL-8-induced leukocyte infiltration into the airway wall.
John
Matthias
M
Department of Pneumology, University Hospital Charité, Schumannstr. 20/21, Berlin 10098, Germany. matthias.john@charite.de
Oltmanns
Ute
U
Binder
Claudia
C
Meiners
Silke
S
Gellert
Klaus
K
Chung
K Fan
KF
Witt
Christian
C
D000730:Androstadienes / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001507:Beclomethasone / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D015536:Down-Regulation; D000068298:Fluticasone; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D018946:Chemokine CCL5; D016209:Interleukin-8; D019819:Budesonide; D000068298:Fluticasone; D001507:Beclomethasone