TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells.

Lipopolysaccharides (LPS), the major components of the wall of gram-negative bacteria, trigger powerful defensive responses in the airways via mechanisms thought to rely solely on the Toll-like receptor 4 (TLR4) immune pathway. Here we show that airway epithelial cells display an increase in intracellular Ca concentration within seconds of LPS application. This response occurs in a TLR4-independent manner, via activation of the transient receptor potential vanilloid 4 cation channel (TRPV4).

Toluene diisocyanate and methylene diphenyl diisocyanate: asthmatic response and cross-reactivity in a mouse model.

Both 2,4-toluene diisocyanate (TDI) and 4,4-methylene diphenyl diisocyanate (MDI) can cause occupational asthma. In this study, we optimized our mouse model of chemical-induced asthma in the C57Bl/6 mice strain using the model agent TDI. Furthermore, we validated MDI in this mouse model and investigated whether cross-reactivity between TDI and MDI is present.

Proteomic Alterations in B Lymphocytes of Sensitized Mice in a Model of Chemical-Induced Asthma.

Introduction And Aim: The role of B-lymphocytes in chemical-induced asthma is largely unknown. Recent work demonstrated that transferring B lymphocytes from toluene diisocyanate (TDI)-sensitized mice into naïve mice, B cell KO mice and SCID mice, triggered an asthma-like response in these mice after a subsequent TDI-challenge. We applied two-dimensional difference gel electrophoresis (2D-DIGE) to describe the "sensitized signature" of B lymphocytes comparing TDI-sensitized mice with control mice.

Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis.

Background: Effective treatments for fibrotic diseases such as idiopathic pulmonary fibrosis are largely lacking. Transforming growth factor beta (TGFβ) plays a central role in the pathophysiology of fibrosis. We hypothesized that bone morphogenetic proteins (BMP), another family within the TGFβ superfamily of growth factors, modulate fibrogenesis driven by TGFβ.

Secreted frizzled related proteins inhibit fibrosis in vitro but appear redundant in vivo.

Background: The pathogenesis of pulmonary fibrosis remains poorly understood. The Wnt signaling pathway regulates fibrogenesis in different organs. Here, we studied the role of two extracellular Wnt antagonists, secreted frizzled-related protein-1 (SFRP1) and frizzled-related protein (FRZB) on lung fibrosis in vitro and in vivo.

B-lymphocytes as key players in chemical-induced asthma.

T-lymphocytes and B-lymphocytes are key players in allergic asthma, with B-lymphocytes producing antigen-specific immunoglobulins E (IgE). We used a mouse model of chemical-induced asthma and transferred B-lymphocytes from sensitized animals into naïve wild type mice, B-lymphocyte knock-out (B-KO) mice or severe combined immunodeficiency (SCID) mice. On days 1 and 8, BALB/c mice were dermally sensitized with 0.

Crucial role of transient receptor potential ankyrin 1 and mast cells in induction of nonallergic airway hyperreactivity in mice.

Rationale: Airway hyperreactivity (AHR) is a key feature of bronchial asthma, and inhalation of irritants may facilitate development of nonallergic AHR. Swimmers exposed to hypochlorite (ClO(-))-containing water show a higher risk of developing AHR. We developed a mouse model in which instillation of ClO(-) before ovalbumin (OVA) induces AHR without bronchial inflammatory cells.

Neutrophil and eosinophil granulocytes as key players in a mouse model of chemical-induced asthma.

Diisocyanates are an important cause of chemical-induced occupational asthma. This type of immunologically mediated asthma is often characterized by a predominant granulocytic inflammation in the airways, rather than an infiltration by lymphocytes. We sought to determine the contribution of granulocytes in the outcome of chemical-induced asthma using general and specific leukocyte depletion strategies in an established mouse model of isocyanate asthma.

Proteome changes in auricular lymph nodes and serum after dermal sensitization to toluene diisocyanate in mice.

Some reactive chemicals, such as diisocyanates, are capable of initiating an allergic response, which can lead to occupational asthma after a latency period. Clinical symptoms such as cough, wheezing, and dyspnea occur only late, making it difficult to intervene at an early stage. So far, most studies using proteomics in lung research have focused on comparisons of healthy versus diseased subjects.

Thrombogenic changes in young and old mice upon subchronic exposure to air pollution in an urban roadside tunnel.

Epidemiological studies indicate that elderly persons are particularly susceptible to the cardiovascular health complications of air pollution, but pathophysiological mechanisms behind the increased susceptibility remain unclear. Therefore, we investigated how continuous traffic-related air pollution exposure affects haemostasis parameters in young and old mice. Young (10 weeks) and old (20 months) mice were placed in an urban roadside tunnel or in a clean environment for 25 or 26 days and markers of inflammation and endothelial cells or blood platelet activation were measured, respectively.

Nano-titanium dioxide modulates the dermal sensitization potency of DNCB.

We determined the ability of a model nanoparticle (NP) (titanium dioxide, TiO(2)) to modulate sensitization induced by a known potent dermal sensitizer (dinitrochlorobenzene) using a variant of the local lymph node assay called lymph node proliferation assay.BALB/c mice received sub-cutaneous injections of vehicle (2.5 mM sodium citrate), TiO(2) NPs (0.

Placental growth factor contributes to bronchial neutrophilic inflammation and edema in allergic asthma.

Placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor 1 (VEGFR1) play an important role in pathological conditions related to angiogenesis, vascular leakage, and inflammation. This study investigated their contributions to inflammation and the formation of edema in allergic asthma. The expression of PlGF and VEGFR1 was measured in induced sputum of patients with asthma (n = 11) and healthy subjects (n = 11), and in bronchial biopsies of house dust mite (HDM)-allergic patients stimulated with HDM allergens.

Airway exposure to hypochlorite prior to ovalbumin induces airway hyperreactivity without evidence for allergic sensitization.

Background: Some epidemiologic studies have indicated that attendance to chlorinated swimming pools is associated with airway hyperreactivity (AHR), allergies and asthma.

Aim: To investigate the effects of sodium hypochlorite (NaClO), the main pool disinfectant, on allergic sensitization and airway inflammation in mice.

Methods: In a first series of experiments, mice were sensitized to ovalbumin (OVA), followed by OVA aerosols with or without prior nasal instillation of NaClO (3ppm active chlorine).

Repeated invasive lung function measurements in intubated mice: an approach for longitudinal lung research.

Invasive lung function measurements are useful tools to describe respiratory disease models in mice but only result in one time-point measurements because of tracheostomy. We explored if intubation may overcome the need for tracheostomy thereby allowing invasive lung function monitoring of individual mice over time. Repeated invasive lung function measurements with Scireq(©) - FlexiVent or Buxco(©) - Forced Pulmonary Maneuvers(®) were performed three times in BALB/c mice with intervals of 10 days.

Successful transfer of chemical-induced asthma by adoptive transfer of low amounts of lymphocytes in a mouse model.

Background: We optimized an adoptive transfer protocol in our mouse model of TDI-induced asthma in order to investigate the mechanisms of this type of occupational asthma.

Methods: On days 1 and 8, BALB/c mice were dermally sensitized with 0.3% TDI or vehicle (acetone/olive oil), and on day 15, they were sacrificed and a cell suspension was made from auricular lymph nodes.

Proteome analysis of multiple compartments in a mouse model of chemical-induced asthma.

Occupational asthma is the principal cause of work-related respiratory disease in the industrial world. Toluene-2,4-diisocyanate (TDI) is one of the most common respiratory sensitizers leading to occupational asthma. Using a mouse model of chemical-induced asthma, we explored proteome changes in multiple compartments of mice sensitized and challenged with TDI or acetone-olive oil (AOO; vehicle).

Choice of mouse strain influences the outcome in a mouse model of chemical-induced asthma.

Background: The development of occupational asthma is the result of interactions between environmental factors and individual susceptibility. We assessed how our model of chemical-induced asthma is influenced by using different mouse strains.

Methodology/principal Findings: On days 1 and 8, male mice of 7 different strains (BALB/c, BP/2, A/J, C57Bl/6, DBA/2, CBA and AKR) were dermally treated with toluene-2,4-diisocyanate (TDI) (0.

Ammonium persulfate can initiate an asthmatic response in mice.

Background: Persulfate salts are the main cause of occupational asthma (OA) in hairdressers. The aim of this study was to verify whether ammonium persulfate ((NH(4))(2)S(2)O(8), AP) is capable of triggering an asthma-like response in mice.

Methods: BALB/c mice were dermally treated on days 1 and 8, with dimethylsulfoxide (DMSO), 1% AP or 5% AP (20 microl/ear).

Oropharyngeal aspiration: an alternative route for challenging in a mouse model of chemical-induced asthma.

Background: To assess the importance of the route of challenge in an existing mouse model of chemical-induced asthma, we replaced intranasal instillation by oropharyngeal aspiration. To our knowledge, oropharyngeal aspiration as a challenge route has not yet been investigated in a mouse model of chemical-induced asthma.

Methods: On days 1 and 8, mice were dermally sensitized with toluene diisocyanate (TDI) (0.

Noninvasive and invasive pulmonary function in mouse models of obstructive and restrictive respiratory diseases.

Pulmonary function analysis is an important tool in the evaluation of mouse respiratory disease models, but much controversy still exists on the validity of some tests. Most commonly used pulmonary function variables of humans are not routinely applied in mice, and the question of which pulmonary function is optimal for the monitoring of a particular disease model remains largely unanswered. Our study aimed to delineate the potential and restrictions of existing pulmonary function techniques in different respiratory disease models, and to determine some common variables between humans and mice.

Is toluene diamine a sensitizer and is there cross-reactivity between toluene diamine and toluene diisocyanate?

Toluene diamine (TDA) is formed when toluene diisocyanate (TDI), a potent sensitizer, comes in contact with an aqueous environment. The sensitizing capacity of TDA and the cross-reactivity between TDI and TDA are unknown. TDA (5-25%) and TDI (0.

Assessment of the sensitization potential of persulfate salts used for bleaching hair.

Background: Persulfate salts have been associated with both allergic contact dermatitis and bronchial asthma. Because there is currently no experimental data available on the sensitizing properties of persulfate salts (ammonium, sodium, and potassium persulfates), we determined their dermal sensitizing capacity, using the murine local lymph node assay (LLNA).

Material And Methods: For three consecutive days, BALB/c mice were dermally treated with ammonium, sodium, or potassium persulfate or with the vehicle alone (dimethyl sulfoxide) on each ear (2 x 25 microl).

Multiple challenges in a mouse model of chemical-induced asthma lead to tolerance: ventilatory and inflammatory responses are blunted, immunologic humoral responses are not.

To improve our mouse model of chemical-induced asthma we compared a single with a multiple intranasal challenge protocol. BALB/c mice received toluene diisocyanate (TDI) or vehicle on each ear (days 1 and 8) with the first challenge by intranasal instillation given on day 15. In a "long" protocol, the mice received 1 to 6 intranasal instillations, with 1-week interval.

How long do the systemic and ventilatory responses to toluene diisocyanate persist in dermally sensitized mice?

Background: Years after removal from exposure, workers with occupational asthma still show respiratory symptoms and airway hyperresponsiveness on re-exposure to the offending agent.

Objective: We investigated the persistence of the respiratory responsiveness to toluene diisocyanate (TDI) in a mouse model.

Methods: BALB/C mice received dermal applications of TDI on days 1 and 8, and a single intranasal instillation of TDI on day 10, 15, 20, 25, 30, 40, 50, 60, or 90.

Immunological determinants of ventilatory changes induced in mice by dermal sensitization and respiratory challenge with toluene diisocyanate.

The objective of the study was to characterize better the immunologic mechanisms underlying a previously developed animal model of chemical-induced asthma. BALB/c and severe combined immunodeficiency disease (SCID) mice received toluene diisocyanate (TDI) or vehicle on each ear on day 1 and/or day 7. On day 10, they were intranasally challenged with TDI or vehicle.