Murine models of hapten-induced asthma

Russjan, Ewelina

doi:10.1016/j.tox.2018.09.001

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…Through the comparison of the effects of chimera with simple equimolar mixture of its structural elements, we also confirmed the hypothesis that two drugs combined into one entity may be characterized by improved therapeutic activity. Indeed, PK20 treatment occurred to be more effective in substantial reduction of inflammatory cell influx, including neutrophils, typical cells for nonallergic asthma [22,24]. Reduced inflammatory cell influx was associated with diminished production of pro-inflammatory cytokines and chemokines in BALF and lung tissue.…”

Section: Discussionmentioning

confidence: 99%

Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma

Russjan

Andrzejewski

Sulejczak

et al. 2019

IJMS

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We examined anti-inflammatory potency of hybrid peptide-PK20, composed of neurotensin (NT) and endomorphin-2 (EM-2) pharmacophores in a murine model of non-atopic asthma induced by skin sensitization with 2,4-dinitrofluorobenzene and intratracheal challenge of cognate hapten. Mice received intraperitoneally PK20, equimolar mixture of its structural elements (MIX), dexamethasone (DEX), or NaCl. Twenty-four hours following hapten challenge, the measurements of airway responsiveness to methacholine were taken. Bronchoalveolar lavage (BALF) and lungs were collected for further analyses. Treatment with PK20, similarly to dexamethasone, reduced infiltration of inflammatory cells, concentration of mouse mast cell protease, IL-1β, IL-12p40, IL-17A, CXCL1, RANTES in lungs and IL-1α, IL-2, IL-13, and TNF-α in BALF. Simple mixture of NT and EM-2 moieties was less potent. PK20, DEX, and MIX significantly decreased malondialdehyde level and secretory phospholipase 2 activity in lungs. Intensity of NF-κB immunoreactivity was diminished only after PK20 and DEX treatments. Neither PK20 nor mixture of its pharmacophores were as effective as DEX in alleviating airway hyperresponsiveness. PK20 effectively inhibited hapten-induced inflammation and mediator and signaling pathways in a manner seen with dexamethasone. Improved anti-inflammatory potency of the hybrid over the mixture of its moieties shows its preponderance and might pose a promising tool in modulating inflammation in asthma.

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Section: Discussionmentioning

confidence: 99%

Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma

Russjan

Andrzejewski

Sulejczak

et al. 2019

IJMS

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“…Haptens are also broadly used in rodent models to investigate exacerbation in airway inflammation. Studies with toluene diisocyanate (TDI), trimellitic anhydride (TMA), dinitrofluorobenzene (DNFB), and picryl chloride (PCL), allowed dissecting the hapten-induced allergy as well as the similarities and differences between the different compounds (44)(45)(46)(47). Rodent models of DNFB, a powerful sensitizer of non-atopic asthma (47), have recently shown increased numbers of macrophages in bronchoalveolar lavage fluid (BALF), tracheal hyper-reactivity and a strong neutrophilic-based lung inflammation that could reflect characteristic features of non-atopic asthma in humans (46,48).…”

Section: Eliciting Allergic Airway Inflammationmentioning

confidence: 99%

Mimicking Antigen-Driven Asthma in Rodent Models—How Close Can We Get?

et al. 2020

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Asthma is a heterogeneous disease with increasing prevalence worldwide characterized by chronic airway inflammation, increased mucus secretion and bronchial hyperresponsiveness. The phenotypic heterogeneity among asthmatic patients is accompanied by different endotypes, mainly Type 2 or non-Type 2. To investigate the pathomechanism of this complex disease many animal models have been developed, each trying to mimic specific aspects of the human disease. Rodents have classically been employed in animal models of asthma. The present review provides an overview of currently used Type 2 vs. non-Type 2 rodent asthma models, both acute and chronic. It further assesses the methods used to simulate disease development and exacerbations as well as to quantify allergic airway inflammation, including lung physiologic, cellular and molecular immunologic responses. Furthermore, the employment of genetically modified animals, which provide an in-depth understanding of the role of a variety of molecules, signaling pathways and receptors implicated in the development of this disease as well as humanized models of allergic inflammation, which have been recently developed to overcome differences between the rodent and human immune systems, are discussed. Nevertheless, differences between mice and humans should be carefully considered and limits of extrapolation should be wisely taken into account when translating experimental results into clinical use.

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“…One day later, the sensitization on the thorax was repeated. DNFB is a small-molecular-weight compound-hapten, that acquires immunogenicity after attachment to the protein carrier [88]. On day 6, the animals were intratracheally challenged with cognate hapten-50 μL of 0.6% DNS (dinitrobenzene sulfonic acid) dissolved in pure water.…”

Section: Inhalationsmentioning

confidence: 99%

Inhalations with Brine Solution from the ‘Wieliczka’ Salt Mine Diminish Airway Hyperreactivity and Inflammation in a Murine Model of Non-Atopic Asthma

Zając

Russjan

Kostrzon

2020

IJMS

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Inhalations with brine solutions are old but underestimated add-ons to pharmacological treatments of inflammatory lung diseases. Although widely used, not all features underlying their action on the respiratory system have been explored. The aim of the present study was to elucidate the mechanism of the beneficial action of inhalations of brine solution from the ‘Wieliczka’ Salt Mine, a Polish health resort, in a murine model of non-atopic asthma. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by an intratracheal challenge of cognate hapten. All animals underwent 12 inhalation sessions with brine solution, pure water or physiological saline. Control mice were not inhaled. We found that brine inhalations reduced, as compared to non-inhaled mice, the typical asthma-related symptoms, like airway hyperreactivity (AHR), the infiltration of pro-inflammatory cells into the bronchial tree, and the inflammation of the airways at the level of pro-inflammatory cytokines IL-1α, IL-1β and IL-6. The level of the anti-inflammatory IL-10 was elevated in brine-inhaled mice. Inhalations with pure water increased AHR, whereas saline had no influence, either on AHR or cytokine concentrations. These observations indicate that inhalations with a brine solution from the ‘Wieliczka’ Salt Mine diminish the asthma-related symptoms, mostly by reducing the inflammatory status and by decreasing AHR.

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Murine models of hapten-induced asthma

Cited by 9 publications

References 40 publications

Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma

Endomorphin-2- and Neurotensin- Based Chimeric Peptide Attenuates Airway Inflammation in Mouse Model of Nonallergic Asthma

Mimicking Antigen-Driven Asthma in Rodent Models—How Close Can We Get?

Inhalations with Brine Solution from the ‘Wieliczka’ Salt Mine Diminish Airway Hyperreactivity and Inflammation in a Murine Model of Non-Atopic Asthma

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