Regulation of ciliary beat frequency by both PKA and PKG in bovine airway epithelial cells

1998 ◽  
Vol 275 (4) ◽  
pp. L827-L835 ◽  
Author(s):  
T. A. Wyatt ◽  
J. R. Spurzem ◽  
K. May ◽  
J. H. Sisson

Ciliary beating is required for the maintenance of lung mucociliary transport. We investigated the role of cyclic nucleotide-dependent protein kinases in stimulating ciliary beat frequency (CBF) in bovine bronchial epithelial cells (BBECs). cAMP-dependent protein kinase (PKA) activity and cGMP-dependent protein kinase (PKG) activity were distinguished after DEAE-Sephacel chromatography of BBEC extracts. cAMP levels and PKA activity are increased in BBECs stimulated with 0.01–1 mM isoproterenol, with a corresponding increase in CBF. cGMP levels and PKG activity are increased in BBECs stimulated with 0.1–10 μM sodium nitroprusside, with a corresponding increase in CBF. Direct protein kinase-activating analogs of cAMP and cGMP (dibutyryl cAMP and 8-bromo-cGMP, respectively) also activate their specific kinases and stimulate CBF. Preincubation of BBECs with inhibitors of PKA or PKG [KT-5720 or Rp-8-( p-chlorophenylthio)-guanosine 3′,5′-cyclic monophosphothioate] results in the inhibition of specific kinase activity as well as in the inhibition of CBF. These studies suggest that the activation of either PKA or PKG can lead to the stimulation of CBF in bovine airway epithelium.

2021 ◽  
Vol 12 ◽  
Author(s):  
Moira L. Aitken ◽  
Ranjani Somayaji ◽  
Thomas R. Hinds ◽  
Maricela Pier ◽  
Karla Droguett ◽  
...  

The role of inflammation in airway epithelial cells and its regulation are important in several respiratory diseases. When disease is present, the barrier between the pulmonary circulation and the airway epithelium is damaged, allowing serum proteins to enter the airways. We identified that human glycated albumin (GA) is a molecule in human serum that triggers an inflammatory response in human airway epithelial cultures. We observed that single-donor human serum induced IL-8 secretion from primary human airway epithelial cells and from a cystic fibrosis airway cell line (CF1-16) in a dose-dependent manner. IL-8 secretion from airway epithelial cells was time dependent and rapidly increased in the first 4 h of incubation. Stimulation with GA promoted epithelial cells to secrete IL-8, and this increase was blocked by the anti-GA antibody. The IL-8 secretion induced by serum GA was 10–50-fold more potent than TNFα or LPS stimulation. GA also has a functional effect on airway epithelial cells in vitro, increasing ciliary beat frequency. Our results demonstrate that the serum molecule GA is pro-inflammatory and triggers host defense responses including increases in IL-8 secretion and ciliary beat frequency in the human airway epithelium. Although the binding site of GA has not yet been described, it is possible that GA could bind to the receptor for advanced glycated end products (RAGE), known to be expressed in the airway epithelium; however, further experiments are needed to identify the mechanism involved. We highlight a possible role for GA in airway inflammation.


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