Changes in Phosphoinositide Turnover in Airway Smooth Muscles and Blood Lymphocytes in Ova Sensitized Guinea Pig Model of Asthma.
Asthma affects approximately 10% of the population in the United States and its prevalence
has almost doubled in the past 20 years. In India, its prevalence varies between 2.4 to 31.14%
from different parts of the country. Airway inflammation, persistent
airway hyperresponsiveness and airway obstruction are the main characteristics of asthma.
Onset of this disease starts with the sensitization to an allergen, followed by IgE-mediated response, mast
cell degranulation, bronchoconstriction and recruitment of
inflammatory cells. In addition, during progression of the disease, structural changes in the airways like; goblet cell hyperplasia, smooth muscle thickening and subepithelial and airway wall fibrosis are known to occur.
Asthma is triggered by various stimuli including virus, environmental
pollutants, tree and weed pollens, cold air, exercise etc. The response of airway
cells to these stimuli is mediated through activation of
distinct transmembrane signaling intermediates. The activation
of protein kinase C signaling pathway is one of the key players in asthma pathogenesis.
Previously, we and others have shown that inhibition of PKC reduces the activation
of lymphocytes, inhibits the expression of Th2 cytokines
by T lymphocytes from asthmatic patients, abolishes airway smooth muscles
constriction, and inhibits the proliferation and
structural changes in airway smooth muscle cells from asthmatic rats.
In another study, inhibition of PKC by calphostin-C, prevented proliferation of bovine
tracheal smooth muscle cells following activation of mannose receptors by β-hexosaminidase
and also abolished Ca2+-dependent and -independent PKC activity20 which
suggests involvement of different isoenzymes of PKC.
Pulm Res Respir Med Open J. 2016; 3(1): 10-18. doi: 10.17140/PRRMOJ-3-125
