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Nerve growth factor mediated SH2‐Bβ/Akt signal pathway activated in allergic airway challenge in mice
Author(s) -
LIU Yuli,
ZHANG Baohui,
ZHANG Shuna,
QI Jinping,
ZHANG Zhenghong,
LIU Libo,
FANG Xiubin
Publication year - 2010
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2009.01648.x
Subject(s) - medicine , protein kinase b , ovalbumin , nerve growth factor , bronchoconstriction , immunology , allergic inflammation , inflammation , endocrinology , signal transduction , asthma , receptor , immune system , biology , microbiology and biotechnology
Background and objective: Nerve growth factor (NGF) contributes to airway inflammation and bronchoconstriction in allergic asthma. The Src homology 2β/serine/threonine kinase (SH2‐Bβ/Akt) pathway is one of the avenues through which NGF regulates the biological activity of pheochromocytoma (PC)12 cells. It has also been reported that NGF upregulates the expression of SH2‐Bβ in the lung tissue of asthmatic mice. The present study investigated the effects of NGF and SH2‐Bβ on Akt activation during allergic airway challenge. Methods: BALB/c mice were sensitized and challenged with ovalbumin. The effects of NGF and SH2‐Bβ on Akt in allergic airway challenge were assessed by intravenously administering anti‐NGF antibody or a mutant of SH2‐Bβ (R555E) to these mice. Pulmonary histological changes were then assessed and the inflammatory cells in the BAL fluid (BALF) were counted. Additionally, phosphorylated Akt (p‐Akt) expression was determined by fluorescence microscopy, western blotting and quantitative RT‐PCR. Airway resistance was also measured using closed‐type body plethysmography. Results: We observed p‐Akt overexpression in the lungs after allergen challenge by fluorescence microscopy, Western blotting and RT‐PCR, as compared with the control. However, after treatment with anti‐NGF or R555E, p‐Akt levels and allergen‐induced airway inflammation were reduced in comparison with those of allergen‐challenged mice. Anti‐NGF and R555E also decreased airway hyperresponsiveness caused by allergen challenge in response to methacholine (MCH). Conclusions: These results suggest that SH2‐Bβ regulation of Akt partly participates in the NGF‐mediated development of allergic airway challenge.