Gingko biloba: A Potential Therapy for Lung Inflammation in Smokers
Prerna Rastogi, John Marentette, Jane McHowat. St. Louis University - School of Medicine, St. Louis, MO
Background: Ginkgo biloba has been used in traditional herbal medicine for several disorders. In this study we demonstrate that Gingkolides decrease inflammatory cell recruitment in the airways. Cigarette smoke causes small airway inflammation and inflammatory cell recruitment, resulting in widepsread damage which may progress to cancer. Platelet-activating factor (PAF) is a membrane phospholipid-derived metabolite formed by activation of calcium-independent phospholipase A2 (iPLA2) and catabolized by PAF acetyl hydrolase (PAF-AH). PAF promotes trans-endothelial and trans-epithelial cell migration and we postulate that increased PAF production in the airways of smokers enhances inflammatory cell recruitment and exacerbates inflammation.
Design: Human small airways epithelial cells (HSAEC) were incubated with cigarette smoke extract (CSE) and PAF-AH activity and PAF accumulation measured. PAF production was inhibited with the iPLA2 inhibitor bromoenol lactone (BEL). Next, we pretreated neutrophils with Gingkolide B, a PAF receptor blocker and measured their ability to adhere to the airway epithelial cell monolayers and transmigrate across them.
Results: Our experiments showed that PAF-AH activity decreased (3.8 + 0.2 to 2.1 + 0.3 nmol/mg protein/min, p<0.05, n=4) and PAF accumulation increased when airway epithelial cells were incubated with cigarette smoke extract (2277 + 87 dpm to 5107 + 203 dpm at 4 hours, p<0.01, n=6). PAF accumulation was blocked with BEL pretreatment. This suggests that increased PAF accumulation is a combination of increased synthesis (iPLA2 activation) and decreased degradation (PAF-AH inhibition). We also observed a significant increase in neutrophil adherence to the airway eppithelial cell monolayers treated with cigarette smoke extract (15 + 5 to 43 + 6%, p<0.01, n=6). Cigarette smoke exposure also increased neutrophil transmigration (3-fold) across the cell monolayer in a basolateral to apical direction. Neutrophil adherence and transmigration was inhibited by pretreating PMN with Ginkgolide B to block the PAF receptor.
Conclusions: Taken together, our data demonstrate that increased accumulation of inflammatory cells in the airways of smokers depends on increased PAF production in the airway epithelium. In addition to smoking cessation, treatment with Ginkgo biloba may be a potential therapy to manage airway inflammation.
Monday, March 4, 2013 1:00 PM
Poster Session II # 261, Monday Afternoon