Premium
Downregulation of NGF attenuates AHR persistence induced by respiratory syncytial virus infection in BALB/c mice (870.3)
Author(s) -
Zang Na,
Zhou Na,
Deng Yu,
Xie Xiaohong,
Xu Fadi,
Liu Enmei
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.870.3
Subject(s) - trif , medicine , immunology , nasal administration , inflammation , respiratory system , downregulation and upregulation , immune system , biology , innate immune system , toll like receptor , biochemistry , gene
RSV infection causes acute morbidity and recurrent wheezing that could persist up to several years, but the relevant mechanisms remain unclear. Because NGF is involved in developing AHR during acute phase of RSV infection, we asked whether RSV infection also induced a chronic AHR in mice, and if so, what role pulmonary NGF played. Mice at day 7, 14, 21, 30 and 60 after intranasal inoculation of RSV were either placed in a whole body plethysmograph to measure their Penh responses to increasing doses of aerosol methacholine or euthanized for collecting BALF to detect pulmonary NGF. We found that AHR and NGF/BDNF were gradually increased and persisted 60 days after RSV infection. To define whether NGF was responsible for the AHR persistence via TLRs‐TRIF signaling pathway, the AHR was tested in other mice after administration of anti‐NGF neutralized antibody (ip) once on day 14 postinfection and resveratrol (inhibitor of TRIF, ip) daily from day 0 to day 21 postinfection, respectively. The RSV‐induced AHR and NGF were markedly attenuated by both treatments. Additionally, RSV infection also produced chronic airway inflammation 60 days postinfection that was diminished by resveratrol but not by anti‐NGF. We conclude that NGF is involved in generating the RSV‐induced AHR probably via activation of TLRs‐TRIF signaling pathway, while the latter but not NGF participates the RSV‐induced chronic airway inflammation.