Changes in Phosphoinositide Turnover in Airway Smooth Muscles and Blood Lymphocytes in Ova Sensitized Guinea Pig Model of Asthma

Abstract

Citation ResearchPage 10 AbstRAct background and Objective: Bronchial asthma has been defined as a combination of reversible airway obstruction, increased airway responsiveness, and airway inflammation. Protein kinase C (PKC) is a primary group of enzymes mediating signal transduction for a wide variety of functions in many different cell types. Its activation has been implicated in various inflammatory diseases. Since PKC activity is regulated by the metabolic pool of phosphoinositides and their turnover. The involvement of these phospholipids in allergic inflammatory responses is, however, yet to be fully determined. To evaluate the changes in phosphoinositide turnover in guinea pig model of asthma and correlation with PKC activity. Methods: Male guinea pigs were sensitized with ovalbumin and day of initial allergen-specific immune response determined by intradermal test. Airway hyperresponsiveness was measured using a plethysmograph. Airway remodeling, content of mucin was assessed histochemically on lung sections, and bronchoalveolar lavaged fluid (BALF) cell composition. Total PKC activity, phosphoinositides were assessed in airway smooth muscles (ASM) and peripheral blood lymphocytes. Results: Compared with control mice, OVA-challenged mice led to enhanced recruitment of inflammatory cells in bronchoalveolar lavage fluid, increases in inflammation scores, collagen accumulation, bronchial wall thickness and inflammatory cytokines. Also, we examined total PKC activity is increased in ASM and lymphocytes isolated from both groups. The levels of phosphoinositide intermediates increased further in both ASM and lymphocyte in Ova-sensitized group as compared to control group. conclusion: Ova exposure aggravated airway inflammation, airway remodelling, activation of inflammatory cytokines, and increases PKC activity in OVA-sensitized and -challenged mice, correlated with total phosphoinositide intermediates increased further in both ASM and lymphocyte.