PI3K Roles in Chronic Asthmatic Airway Remodeling

초록

Purpose: Phosphoinositide 3-kinase(P13K) is a important chemokine to modulate the migration of eosinophils, T cells, macrophages and neutrophils that develop the allergic inflammation in asthmatic lung. To determine how the P13K affect to airway remodeling in chronic asthma model mouse. Method: We made the chronic asthma model in P13Kγ-knock out mice and wild type. Determination of smooth muscle thickness, and quantitation of airway mucus expression and TGF-β were taken. Result: There were 25 PI3Kγ(-/-) mice(10; ova challenged, 15; PBS challenged) and 29 controlled WT mice(15; ova, 14; PBS). The decrease in airway responsiveness was evident in OVA challenged KO mice compared to WT mice(p<0.001). The munber of BAL eosinophils in OVA challenged PI3KγKO mice were still significantly decreased comparing to WT OVA challenged mice (273.00±32.91 vs 614.60±100.20 BAL eosinophils)(p<0.01). The absolute number of eosinophils in peripheral blood and bone marrow of KO mice sensitized to OVA was not significantly different with OVA challenged WT mice. The eosinophil numbers in peribronchial area which stained positive with major basic protein staining was significantly reduced in KO mice compared to WT mice challenged with OVA(39.92±1.98 vs 52.24±3.72)(p<0.001). KO mice with OVA challenge significantly reduced the area of trichrome staining compared to WT mice with OVA(2.1790 ± 0.1358 vs 2.6660 ± 0.1242 m2/m circumference of bronchiole)(p<0.05). KO mice challenged with OVA significantly reduced the content of collagen compared to WT mice challenged with OVA(16.82±1.66 vs 21.78±2.33 ㎍/lung)(p<0.05). Repetitive OVA challenges did not significantly reduce the amount of TGF-β in KO mice compared to WT mice( 0.6692±0.0055 vs 0.7057±0.0033 ng/ml) Conclusion: In a mouse model of chronic ovalbumin-induced asthma, PI3Kγ dericiency is a important factor to decrease the peribronchial fibrosis resulting from decreased eosinophil influx into the lung.