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Blockage of nerve growth factor modulates T cell responses and inhibits allergic inflammation in a mouse model of asthma

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Abstract

Objective

Blockage of nerve growth factor (NGF) by anti-NGF antibodies can inhibit allergic airway hyper-responsiveness in mice. This study was aimed at determining the mechanisms underlying the action of anti-NGF in vivo.

Methods

BALB/c mice were sensitized with ovalbumin (OVA) and treated with anti-NGF. At 1 day after the last challenge, their airway responsiveness and inflammation were examined and the levels of cytokine and transcription factor mRNA transcripts in the lungs and cytokines in the bronchoalveolar lavage fluid were determined. The frequency of different functional T cells and the levels of serum OVA-specific antibodies were measured.

Results

OVA challenge induced severe airway resistance, inflammation, higher levels of IL-4, TNFα, IL-17A, TGFβ, GATA-3 and RORγT expression and increased Th2 and Th17 cells and IgE responses, but decreased IFNγ and IL-10 responses, T-bet and Foxp3 expression and Th1 and Tregs. Treatment with anti-NGF significantly reduced allergic airway resistance and inflammation, up-regulated IFNγ, IL-10, TGFβ, T-bet, and Foxp3 expression, increased Th1 and Tregs, but down-regulated IL-4, TNFα, IL-17A, RORγT and GATA-3 expression and reduced Th2 and Th17 cells, accompanied by increased serum IgG2a.

Conclusions

Anti-NGF inhibits allergic airway inflammation by modulating the balance of pro- and anti-asthmatic T cell responses in the lungs of mice.

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Abbreviations

AHR:

Airway hyperresponsiveness

APC:

Antigen presenting cells

BALF:

Bronchoalveolar lavage fluid

H&E:

Hematoxylin and eosin

HRP:

Horseradish peroxidase

NGF:

Nerve growth factor

OVA:

Ovalbumin

TMB:

Tetramethylbenzidine

WBC:

White blood cells

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Conflict of interest

All of the authors state no conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Norman Bethune College of Medicine, Jilin University, 130021, Changchun, China

    Yingli Jin

  2. Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, 130021, Changchun, China

    Yan Shi

  3. The First Hospital of Jilin University, 130021, Changchun, China

    Weiying Guo, Chaoying Liu & Xiaohong Lv

  4. China-Japan Union Hospital of Jilin University, 130033, Changchun, China

    Libo Chen

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  1. Yan Shi
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Correspondence to Yingli Jin.

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Responsible Editor: Michael Parnham.

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Shi, Y., Jin, Y., Guo, W. et al. Blockage of nerve growth factor modulates T cell responses and inhibits allergic inflammation in a mouse model of asthma. Inflamm. Res. 61, 1369–1378 (2012). https://doi.org/10.1007/s00011-012-0538-3

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  • DOI: https://doi.org/10.1007/s00011-012-0538-3

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