Tag: pathogenesis

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Convergence of air pollutant-induced redox-sensitive signals in the dendritic cells contributes to asthma pathogenesis.

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Convergence of air pollutant-induced redox-sensitive signals in the dendritic cells contributes to asthma pathogenesis.

Toxicol Lett. 2015 May 27;

Authors: Li N, Buglak N

Abstract
Exposure to airborne particulate matter (PM) is a major risk factor for allergic airway inflammation such as asthma. Many of the PM components (i.e., polycyclic aromatic hydrocarbons and metals) are redox-active and capable of inducing cellular oxidative stress and injuries including inflammation and cell death. Airway epithelial cells and antigen-presenting dendritic cells (DC) are the major and direct targets of inhaled PM. The epithelial cells can further enhance the DC response to allergen and PM through several immune regulatory cytokines including thymic stromal lymphopoietin (TSLP), IL-33, and IL-25. Among these cytokines TSLP is particularly relevant to the mechanisms by which particulate air pollutants contribute to asthma pathogenesis. Studies have found that TSLP released by PM-exposed human airway epithelial cells could polarize the DC towards a T-helper 2 immune response, which is one of the key immunological mechanisms in asthma pathogenesis. The convergence of regulatory signals generated by PM-induced oxidative stress in DC and the interactions among them may be one of the major mechanisms that are specifically related to the contribution of PM towards asthma pathogenesis.

PMID: 26026960 [PubMed – as supplied by publisher]

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Are mouse models of asthma appropriate for investigating the pathogenesis of airway hyper-responsiveness?

Are mouse models of asthma appropriate for investigating the pathogenesis of airway hyper-responsiveness?

Front Physiol. 2012;3:312

Authors: Kumar RK, Foster PS

Abstract
Whether mouse models of chronic asthma can be used to investigate the relationship between airway inflammation/remodeling and airway hyper-responsiveness (AHR) is a vexed question. It raises issues about the extent to which such models replicate key features of the human disease. Here, we review some of the characteristic pathological features of human asthma and their relationship to AHR and examine some limitations of mouse models that are commonly used to investigate these relationships. We compare these conventional models with our mouse model of chronic asthma involving long-term low-level inhalational challenge and review studies of the relationship between inflammation/remodeling and AHR in this model and its derivatives, including models of an acute exacerbation of chronic asthma and of the induction phase of childhood asthma. We conclude that while extrapolating from studies in mouse models to AHR in humans requires cautious interpretation, such experimental work can provide significant insights into the pathogenesis of airway responsiveness and its molecular and cellular regulation.

PMID: 23060800 [PubMed – in process]

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The effect of unilateral adrenalectomy on transformation of adrenal medullary chromaffin cells in vivo: a potential mechanism of asthma pathogenesis.

The effect of unilateral adrenalectomy on transformation of adrenal medullary chromaffin cells in vivo: a potential mechanism of asthma pathogenesis.

PLoS One. 2012;7(9):e44586

Authors: Hu CP, Zou YQ, Feng JT, Li XZ

Abstract
BACKGROUND: Decreased epinephrine (EPI) is an important underlying factor of bronchoconstriction in asthma. Exogenous ?(2)-adrenergic receptor agonist is one of the preferred options to treat asthma. We previously showed that this phenomenon involved adrenal medullary chromaffin cell (AMCC) transformation to a neuron phenotype. However, the underlying molecular mechanism is not fully understood. To further explore this, an asthmatic model with unilateral adrenalectomy was established in this study.
METHODOLOGY/PRINCIPAL FINDINGS: Thirty-two rats were randomly into four groups (n?=?8 each) control rats (controls), unilateral adrenalectomy rats (surgery-control, s-control), asthmatic rats (asthma), unilateral adrenalectomy asthmatic rats (surgery-induced asthma, s-asthma). Asthmatic rats and s-asthmatic rats were sensitized and challenged with ovalbumin (OVA). The pathological changes in adrenal medulla tissues were observed under microscopy. EPI and its rate-limiting enzyme, phenylethanolamine N-methyl transferase (PNMT), were measured. Peripherin, a type III intermediate filament protein, was also detected in each group. The asthmatic rats presented with decreased chromaffin granules and swollen mitochondria in AMCCs, and the s-asthmatic rats presented more serious pathological changes than those in asthmatic rats and s-control rats. The expressions of EPI and PNMT in asthmatic rats were significantly decreased, as compared with levels in controls (P<0.05), and a further decline was observed in s-asthmatic rats (P<0.05). The expression of peripherin was higher in the asthmatic rats than in the controls, and the highest level was found in the s-asthmatic rats (P<0.05).
CONCLUSION/SIGNIFICANCE: Compared with asthmatic rats and s-control rats, the transformation tendency of AMCCs to neurons is more obvious in the s-asthmatic rats. Moreover, this phenotype alteration in the asthmatic rats is accompanied by reduced EPI and PNMT, and increased peripherin expression. This result provides further evidence to support the notion that phenotype alteration of AMCCs contributes to asthma pathogenesis.

PMID: 22957086 [PubMed – in process]

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