Nerve growth factor mediated SH2-Bβ/Akt signal pathway activated in allergic airway challenge in mice

  1. Yuli LIU1,
  2. Baohui ZHANG1,
  3. Shuna ZHANG2,
  4. Jinping QI1,
  5. Zhenghong ZHANG1,
  6. Libo LIU1,
  7. Xiubin FANG1,*

Article first published online: 23 NOV 2009

DOI: 10.1111/j.1440-1843.2009.01648.x

Issue

Respirology

Respirology

Volume 15, Issue 1, pages 80–87, January 2010

Additional Information

How to Cite

LIU, Y., ZHANG, B., ZHANG, S., QI, J., ZHANG, Z., LIU, L. and FANG, X. (2010), Nerve growth factor mediated SH2-Bβ/Akt signal pathway activated in allergic airway challenge in mice. Respirology, 15: 80–87. doi: 10.1111/j.1440-1843.2009.01648.x

Author Information

  1. 1

    Department of Neurobiology, College of Basic Medicine, China Medical University and

  2. 2

    Institute of Respiratory Diseases, First Affiliated Hospital of China Medical University, Shengyang, Liaoning Province, China

*Xiubin Fang, Department of Neurobiology, College of Basic Medicine, China Medical University, Shengyang, Liaoning Province 110001, China. Email: xbfang@hotmail.com

Publication History

  1. Issue published online: 27 DEC 2009
  2. Article first published online: 23 NOV 2009
  3. Received 7 January 2009; invited to revise 9 February 2009, 26 May 2009; revised 4 May 2009, 14 June 2009; accepted 15 June 2009. (Associate Editor: Martin Kolb).

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Keywords:

  • allergy;
  • Bagg albino/c mouse;
  • nerve growth factor;
  • serine/threonine kinase;
  • Src homology 2β

The study investigated the effects of NGF and SH2-Bβ on Akt activation during allergic airway challenge using BALB/c mice sensitized with ovalbumin. The results indicate that the SH2-Bβ regulation of Akt participates in the NGF-mediated allergic airway response and blocking NGF and SH2-Bβ may be a potential therapeutic approach for asthma.

ABSTRACT

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.

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