Levels Of Eotaxin In Bronchoalveolar Lavage Fluid Research Articles

Diospyros blancoi Attenuates Asthmatic Effects in a Mouse Model of Airway Inflammation

Asthma is a complex disease linked to various pathophysiological events, including proteinase activity. In this study, we examined whether a Diospyros blancoi methanolic extract (DBE) exerts protective effects on allergic asthma in a murine asthma model. To investigate the specific role of DBE, we employed a murine model of allergic airway inflammation. BALB/c mice sensitized and challenged with ovalbumin (OVA) were orally administered 20 or 40mg/kg DBE for 3days during OVA challenge. DBE induced significant suppression of the number of OVA-induced total inflammatory cells, including eosinophils, macrophages, and lymphocytes, in bronchoalveolar lavage fluid (BALF). Moreover, treatment with DBE led to significant decreases in interleukin (IL)-4, IL-5, and eotaxin levels in BALF and OVA-specific immunoglobulin (Ig)E and IgG1 levels in serum. Histological examination of lung tissue revealed marked attenuation of allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. Additionally, DBE suppressed matrix metalloproteinase-9 activity and induced heme oxygenase-1 expression. The present findings collectively suggest that DBE exhibits anti-inflammatory activity in an airway inflammation mouse model, supporting its therapeutic potential for the treatment of allergic bronchial asthma.

Critical role of IL-17R signaling in granulocyte recruitment and airway hyperreactivity in an Aspergillus model of asthma (96.7)

Abstract Rationale IL-17 is a proinflammatory cytokine that enhances neutrophil recruitment in response to allergen in murine lung. In an Aspergillus fumigatus (Af)-induced asthma model, wild-type C57BL/6 mice develop bronchial inflammation and hyperreactivity. We hypothesized that, compared to C57BL/6, Af sensitized IL-17R KO mice would have reduced neutrophil recruitment to the lung, airway resistance and hyperreactivity. Methods C57BL/6 and IL-17R KO male mice, 6–8 wk old, were sensitized intraperitoneally with 40 ug Af extract and 2 mg Al(OH)3 on days 0 and 7, and intratracheally with 25 ug Af on days 21, 22, and 23. Bronchoalveolar lavage (BAL) differential cell counts and cytokine analysis were done at 24 and 72 hr. Flexivent was performed at 24 hr to assess airway physiology. Results WT mice had significant influx of both neutrophils and eosinophils in response to Af at 24 hr. In contrast, IL-17R KO mice showed reduced neutrophil and eosinophil emigration to the lung which was associated with lower KC and eotaxin levels in BAL fluid. Furthermore, Flexivent data showed lower airway resistance and bronchial hyperreactivity in IL-17R KO mice. Conclusion Our findings in Af treated IL-17R KO mice of decreased pulmonary neutrophil and eosinophil recruitment at 24 hr suggest that IL-17 promotes granulocyte recruitment as well as airway hyperreactivity. Funding: NHLBI

Anti-inflammatory effects of LY294002, a PI3K inhibitor, in a mouse model of asthma

Rationale Phosphatidylinositol 3-OH inase (PI3K) signaling cascade plays a pivotal role in the activation of inflammatory cells. The purpose of this study was to investigate the effects of LY294002, a specific PI3K inhibitor, on airway inflammation in an in vivo mouse model of asthma. Methods Mice were actively sensitized by intraperitoneal injections of ovalbumin (OVA) and challenged by aerosolized OVA. Airway hyperresponsiveness was measured using a single-chamber whole-body plethysmograph, airway inflammation with influx of eosinophils was measured using differential cell counting and histological examination, and elevation in cytokine and chemokine levels in bronchoalveolar lavage (BAL) fluid was determined using ELISA. Results LY294002 (1.625, 3.25 and 7.5 mg/kg) given intratracheally significantly inhibited OVA-induced airway hyperresponsiveness to inhaled methacholine in a dose-dependent manner (p<0.05). LY294002 at 7.5 mg/kg also markedly (p<0.05) attenuated OVA-induced increase in eosinophil count in BAL fluid and pulmonary eosinophilia in H&E stained lung section, and elevation of IL-13 and eotaxin levels in BAL fluid. Conclusions These results implicate that inhibition of PI3K signaling cascade may have therapeutic potential for allergic airway inflammation.