Nerve growth factor is released by IL-1  and induces hyperresponsiveness of the human isolated bronchus

Frossard, Nelly

doi:10.1183/09031936.05.00047804

Cited by 51 publications

(35 citation statements)

References 39 publications

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“…The C57BL/6 mice, which are often reported to have more of a Th1 bias as compared with the Th2 bias of BALB/c mice (19,20), have higher levels of IL-5 and IL-13 ( Figure 3) in the BALF, which is followed by higher numbers of eosinophils later in the inflammatory response. Nerve growth factor, although not strictly a cytokine, has been proposed as a mediator of AHR in airway tissue (21,22). We found that it was sharply elevated in the 14-to 24-day time period after inoculation in both strains of mice ( Figure 4A), which may imply a role in the later onset of AHR.…”

Section: The General Immune Response To Pneumocystis Is Strain Specificmentioning

confidence: 56%

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

Swain

Meissner²,

Siemsen³

et al. 2012

Am J Respir Cell Mol Biol

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It is widely held that exposure to pathogens such as fungi can be an agent of comorbidity, such as exacerbation of asthma or chronic obstructive pulmonary disease. Although many studies have examined allergic responses to fungi and their effects on pulmonary function, the possible pathologic implications of the early innate responses to fungal pathogens have not been explored. We examined early responses to the atypical fungus Pneumocystis in two common strains of mice in terms of overall immunological response and related pathology, such as cell damage and airway hyperresponsiveness (AHR). We found a strong strain-specific response in BALB/c mice that included recruitment of neutrophils, NK, NKT, and CD4 T cells. This response was accompanied by elevated indicators of lung damage (bronchoalveolar lavage fluid albumin and LDH) and profound AHR. This early response was absent in C57BL/6 mice, although both strains exhibited a later response associated with the clearance of Pneumocystis. We found that this AHR could not be attributed exclusively to the presence of recruited neutrophils, NKT, NK, or CD4 cells or to the actions of IFN-g or IL-4. However, in the absence of STAT6 signaling, AHR and inflammatory cell recruitment were virtually absent. Gene expression analysis indicated that this early response included activation of several transcription factors that could be involved in pulmonary remodeling. These results show that exposure to a fungus such as Pneumocystis can elicit pulmonary responses that may contribute to morbidity, even without prior sensitization, in the context of certain genetic backgrounds.Keywords: STAT6; airway hyperresponsiveness; Pneumocystis; pulmonary inflammation; strain-specificThe immunological response to respiratory pathogens is normally calibrated to eliminate an infection without causing overt collateral damage to the respiratory tissue. In spite of this, an overexuberant or misdirected immune response can have pathological outcomes. This can range from phenomena that are transient and typically moderate, such as elevated airway hyperresponsiveness (AHR), to those that are permanent and progressive, such as pulmonary fibrosis. The health effects of these immunological responses depend on the context of the infection; those that are comorbid with other acute or chronic pulmonary conditions may incite serious respiratory distress in that context when otherwise they might have little noticeable effect.One area in which the effects of comorbid respiratory illnesses are especially relevant is that of exacerbation of preexisting asthma or chronic obstructive pulmonary disease (COPD). Many potential pathogens have been implicated as causing exacerbation; the most well known are various viruses, including rhinovirus, metapneumovirus, and respiratory syncytial virus (1). Several respiratory bacteria, most notably the atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae, have also been implicated in the exacerbation of asthma symptoms (2). Common fungi have also been widely imp...

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Section: The General Immune Response To Pneumocystis Is Strain Specificmentioning

confidence: 56%

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

Swain

Meissner²,

Siemsen³

et al. 2012

Am J Respir Cell Mol Biol

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“…In addition, AHR is observed after in vitro NGF pre-treatment of guinea pig (de Vries et al, 2001), ferret (Wu & Dey, 2006) or human bronchi (Frossard et al, 2005). AHR is reduced in vivo after administration of a pan-Trk receptor decoy in a mouse model of asthma (Nassenstein et al, 2006), or of the TrkA kinase inhibitor K252a in a guinea pig model of asthma (de Vries et al, 2006), thus showing involvement of the TrkA receptor in NGF-induced AHR.…”

Section: Ngf Trka and Tissue Hyperresponsiveness 521 Asthmamentioning

confidence: 87%

Expression and Role of the TrkA Receptor in Pulmonary Inflammatory Diseases

Freund-Michel¹,

Müller²,

Frossard³

2011

Inflammatory Diseases - A Modern Perspective

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“…Various visceral epithelia are known to produce neurotrophins which were initially speculated to regulate tissue innervation [32] and autocrine functions of neurotrophins are increasingly being described. For example, NGF production is increased during inflammatory processes that are accompanied by epithelium damage in asthma [17,33], infections [34] and sarcoidosis [35].…”

Section: Discussionmentioning

confidence: 99%

Nerve growth factor enhances Clara cell proliferation after lung injury

Sonar¹,

Schwinge²,

Kılıç³

et al. 2010

European Respiratory Journal

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The lung epithelia facilitate wound closure by secretion of various cytokines and growth factors. Nerve growth factor (NGF) has been well described in airway inflammation; however, its likely role in lung repair has not been examined thus far.To investigate the repair function of NGF, experiments were performed in vitro using cultured alveolar epithelial cells and in vivo using a naphthalene-induced model of Clara epithelial cell injury.Both in vitro and in vivo experiments revealed airway epithelial cell proliferation following injury to be dependent on NGF and the expression of its receptor, tropomyosin-receptor-kinase A. Additionally, NGF also augmented in vitro migration of alveolar type II cells. In vivo, transgenic mice over-expressing NGF in Clara cells (NGFtg) did not reveal any proliferation or alteration in Clara cell phenotype. However, following Clara cell specific injury, proliferation was increased in NGFtg and impaired upon inhibition of NGF. Furthermore, NGF also promoted the expression of collagen I and fibronectin in vitro and in vivo during repair, where significantly higher levels were measured in re-epithelialising NGFtg mice.Our study demonstrates that NGF promotes the proliferation of lung epithelium in vitro and the renewal of Clara cells following lung injury in vivo.

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Nerve growth factor is released by IL-1 and induces hyperresponsiveness of the human isolated bronchus

Cited by 51 publications

References 39 publications

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

Expression and Role of the TrkA Receptor in Pulmonary Inflammatory Diseases

Nerve growth factor enhances Clara cell proliferation after lung injury

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