Background: Asthma is a chronic inflammatory disease of the mucosa and is associated with excess TH2 cytokines, eotaxin, prostaglandin D2 (PGD2) and eosinophilia in the lungs. Previous studies have emphasized that the N-terminal peptide of annexin 1 (peptide Ac2-26) can inhibit mast cell degranulation, antigen-induced eotaxin release as well as the accumulation of both neutrophils and eosinophils in a model of rat pleurisy. The purpose of this study was to demonstrate anti-asthmatic effects of Ac2-26 in an asthma model and to explore possible mechanisms involved. Methods: The effect of Ac2-26 on TH2 cytokine release, eotaxin production, PGD2 levels and the development of pulmonary eosinophilic inflammation was compared with glucocorticoids in an asthmatic rat model. The study was conducted on rats sensitized and challenged with ovalbumin and plethysmography measured airway responsiveness. Bronchoalveolar lavage (BAL) histopathology and the levels of cytokines, chemokines as well as PGD2 were examined. Results: Our results showed that Ac2-26 suppressed the accumulation of eosinophils in airways, reduced IL-4, IL-5, IL-13, PGD2 and eotaxin levels in the BAL fluid, and lowered the expression of CRTH2. Exogenous PGD2 significantly attenuated the biological effects of Ac2-26. Conclusion: These results indicated that Ac2-26 exerted broad inhibitory effects on airway inflammation and hyperresponsiveness in a rat model of asthma. Exogenous PGD2 reversed the inhibitory effects of AC2-26 on eosinophil recruitment. Ac2-26 exhibited anti-asthmatic, immunomodulatory activity that was substantially mediated by decreasing PGD2 production and its CRTH2 receptor expression in vivo.

Keywords:
Asthma, Annexin 1, Ac2-26, Prostaglandin D2, Eosinophil recruitment
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© 2010 S. Karger AG, Basel
2010
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