Document Detail


Annexin 1-derived peptide Ac2-26 inhibits eosinophil recruitment in vivo via decreasing prostaglandin D₂.
MedLine Citation:
PMID:  20733322     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Lian-ming Wang; Wen-hui Li; Yong-chen Xu; Qiang Wei; Hong Zhao; Xiao-feng Jiang
Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2010-08-24
Journal Detail:
Title:  International archives of allergy and immunology     Volume:  154     ISSN:  1423-0097     ISO Abbreviation:  Int. Arch. Allergy Immunol.     Publication Date:  2011  
Date Detail:
Created Date:  2011-01-13     Completed Date:  2011-03-03     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  9211652     Medline TA:  Int Arch Allergy Immunol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  137-48     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 S. Karger AG, Basel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Annexin A1 / pharmacology*
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Asthma / drug therapy*,  immunology*
Bronchial Hyperreactivity / drug therapy,  immunology*
Bronchoalveolar Lavage Fluid / cytology,  immunology
Cell Count
Cytokines / analysis
Dinoprostone / antagonists & inhibitors*,  immunology
Dose-Response Relationship, Immunologic
Eosinophils / drug effects,  immunology*
Female
Immunoglobulin E / blood,  immunology
Immunohistochemistry
Male
Methacholine Chloride / pharmacology
Peptides / pharmacology*
Plethysmography
Rats
Rats, Wistar
Specific Pathogen-Free Organisms
Statistics, Nonparametric
Chemical
Reg. No./Substance:
0/Annexin A1; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Cytokines; 0/Peptides; 0/annexin A1 peptide (2-26); 0W5ETF9M2K/Methacholine Chloride; 37341-29-0/Immunoglobulin E; K7Q1JQR04M/Dinoprostone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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