Glucocorticoids inhibited airway hyperresponsiveness through downregulation of CPI-17 in bronchial smooth muscle

Eur J Pharmacol. 2008 Sep 4;591(1-3):231-6. doi: 10.1016/j.ejphar.2008.06.021. Epub 2008 Jun 11.


Glucocorticoids are the most effective anti-inflammatory treatment for asthma, and inhaled corticosteroids are the most effective long-term control therapy for persistent asthma. In the present study, to determine the mechanism of the inhibitory effect of glucocorticoids on airway hyperresponsiveness, the effects of glucocorticoids on the expression and activation of PKC-potentiated protein phosphatase 1 inhibitory protein of 17 kDa (CPI-17) were examined in bronchial smooth muscles of antigen-induced airway hyperresponsive rats. Repeated antigen inhalation to animals sensitized with DNP-Ascaris antigen caused a marked bronchial smooth muscle hyperresponsiveness to acetylcholine, accompanied by upregulation and acetylcholine-induced activation of CPI-17 to result in an increase in myosin light chain (MLC) phosphorylation. Treatment with glucocorticoids (prednisolone or beclomethasone, 10 mg/kg, i.p., respectively) significantly inhibited the airway hyperresponsiveness, and markedly reduced both the protein and mRNA levels of CPI-17 in bronchial smooth muscle. The acetylcholine-induced activation of CPI-17, i.e., phosphorylation of CPI-17, was also significantly inhibited by glucocorticoids. Glucocorticoids also prevented the augmented acetylcholine-induced MLC phosphorylation observed in the airway hyperresponsive rats. Therefore, glucocorticoids might inhibit the airway hyperresponsiveness through the inhibition of overexpression and activation of CPI-17.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Ascaris / immunology
  • Beclomethasone / pharmacology
  • Bronchi / drug effects
  • Bronchi / physiopathology
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchial Hyperreactivity / physiopathology
  • Down-Regulation / drug effects*
  • Glucocorticoids / pharmacology*
  • Male
  • Muscle Proteins / drug effects*
  • Muscle Proteins / metabolism
  • Myosin Light Chains / metabolism
  • Phosphoproteins / drug effects*
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Prednisolone / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar


  • Glucocorticoids
  • Muscle Proteins
  • Myosin Light Chains
  • Phosphoproteins
  • Ppp1r14a protein, rat
  • RNA, Messenger
  • Prednisolone
  • Beclomethasone
  • Acetylcholine