Nerve growth factor mediated SH2-Bbeta/Akt signal pathway activated in allergic airway challenge in mice.
OBJECTIVE
Nerve growth factor (NGF) contributes to airway inflammation and bronchoconstriction in allergic asthma. The Src homology 2beta/serine/threonine kinase (SH2-Bbeta/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-Bbeta in the lung tissue of asthmatic mice. The present study investigated the effects of NGF and SH2-Bbeta on Akt activation during allergic airway challenge.


METHODS
BALB/c mice were sensitized and challenged with ovalbumin. The effects of NGF and SH2-Bbeta on Akt in allergic airway challenge were assessed by intravenously administering anti-NGF antibody or a mutant of SH2-Bbeta (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-Bbeta regulation of Akt partly participates in the NGF-mediated development of allergic airway challenge.
Liu
Yuli
Y
Department of Neurobiology, College of Basic Medicine, China Medical University, Shengyang, Liaoning Province 110001, China.
Zhang
Baohui
B
Zhang
Shuna
S
Qi
Jinping
J
Zhang
Zhenghong
Z
Liu
Libo
L
Fang
Xiubin
X
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000378:metabolism*; D003251:Constriction, Pathologic; D005260:Female; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C115327:Sh2bpsm1 protein, mouse; D016210:Methacholine Chloride; D010047:Ovalbumin; D020932:Nerve Growth Factor; D051057:Proto-Oncogene Proteins c-akt