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

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.

• Authors: Yan Shi, Yingli Jin, Weiying Guo, Libo Chen, Chaoying Liu, Xiaohong Lv
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 61 Issue 12 Pg. 1369-78 (Dec 2012) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 22871964 (Publication Type: Journal Article)

Chemical References

• Allergens
• Antibodies
• Cytokines
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• GATA3 Transcription Factor
• Gata3 protein, mouse
• Immunoglobulin G
• Nuclear Receptor Subfamily 1, Group F, Member 3
• RNA, Messenger
• T-Box Domain Proteins
• T-box transcription factor TBX21
• Immunoglobulin E
• Ovalbumin
• Nerve Growth Factor

Topics

• Allergens
• Animals
• Antibodies (pharmacology)
• Asthma (blood, chemically induced, immunology)
• Bronchial Hyperreactivity (blood, chemically induced, immunology)
• Cytokines (immunology)
• Disease Models, Animal
• Female
• Forkhead Transcription Factors (genetics)
• GATA3 Transcription Factor (genetics)
• Immunoglobulin E (blood)
• Immunoglobulin G (blood)
• Mice
• Mice, Inbred BALB C
• Nerve Growth Factor (antagonists & inhibitors, immunology)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics)
• Ovalbumin
• Pneumonia (blood, chemically induced, immunology)
• RNA, Messenger (metabolism)
• T-Box Domain Proteins (genetics)
• T-Lymphocytes (drug effects, immunology)