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Inhibitory effects of anti-immunoglobulin E antibodies on airway remodeling in a murine model of chronic asthma.

AbstractBACKGROUND:
Airway remodeling is one of the cardinal features of asthma and is thought to play a pivotal role in refractory or persistent asthma. Immunoglobulin E (IgE) has a major effect on the pathogenesis of asthma. The aim of this study was to investigate the effects of anti-IgE antibody not only on airway inflammation and bronchial hyperresponsiveness, but also on airway remodeling in a murine model of chronic asthma.
METHODS:
The authors developed a mouse model of chronic asthma in which ovalbumin (OVA)-sensitized female BALB/c-mice were exposed to intranasal OVA administration twice a week for 3 months. Anti-IgE antibodies were administered intravenously starting on the 38th day and once a month thereafter for 3 months during the intranasal OVA challenge.
RESULTS:
Mice that were chronically exposed to OVA developed sustained eosinophilic airway inflammation and airway hyperresponsiveness (AHR) to methacholine and showed increased levels of collagen, hydroxyproline, and alpha-smooth muscle actin, as compared with control mice. Treatment with anti-IgE antibody inhibited the development of AHR, eosinophilic inflammation, and airway remodeling. Moreover, anti-IgE antibody treatment reduced the levels of interleukin (IL)-5 and IL-13 in the bronchoalveolar lavage fluids, although it did not affect the levels of IL-10, transforming growth factor-beta, and activin A.
CONCLUSION:
These results suggest that anti-IgE antibody treatment modulates the airway inflammation and remodeling associated with chronic allergen challenge. The inhibition of inflammation may be related to the regulation of Th2 cytokines. However, the mechanisms underlying the blocking of airway remodeling by anti-IgE antibody remain to be elucidated.
AuthorsJi Young Kang, Jin Woo Kim, Ju Sang Kim, Seung Joon Kim, Sang Haak Lee, Soon Suk Kwon, Young Kyoon Kim, Hwa Sik Moon, Jeong Sup Song, Sung Hak Park, Sook Young Lee
JournalThe Journal of asthma : official journal of the Association for the Care of Asthma (J Asthma) Vol. 47 Issue 4 Pg. 374-80 (May 2010) ISSN: 1532-4303 [Electronic] England
PMID20528589 (Publication Type: Journal Article)
Chemical References
  • Actins
  • Antibodies, Anti-Idiotypic
  • Cytokines
  • anti-IgE antibodies
  • Immunoglobulin E
  • Ovalbumin
  • Collagen
  • Hydroxyproline
Topics
  • Actins (biosynthesis)
  • Airway Remodeling (drug effects)
  • Animals
  • Antibodies, Anti-Idiotypic (pharmacology)
  • Asthma (immunology, physiopathology)
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid (immunology)
  • Chronic Disease
  • Collagen (biosynthesis)
  • Cytokines (biosynthesis)
  • Eosinophils (drug effects, metabolism)
  • Female
  • Hydroxyproline (biosynthesis)
  • Immunoglobulin E (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin

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