Inhibition of Acidic Mammalian Chitinase by RNA Interference Suppresses Ovalbumin-Sensitized Allergic Asthma

Yang, Ching-Jen; Liu, Yu-Kuo; Liu, Chao-Lin; Shen, Chia-Ning; Kuo, Ming‐Ling; Su, Chi-Wen; Tseng, Ching Ping; Yen, Tzu‐Chen; Shen, Chia–Rui

doi:10.1089/hum.2008.092

Cited by 50 publications

(44 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While we do not observe an increase in overall HDM uptake by pulmonary DCs following blockade of PD-L2 in vivo , it is possible that PD-L2 blockade may subtly regulate the ability of DCs to take up or present specific allergenic peptides. In primary murine tracheal epithelial cells, IL-12 also inhibited the IL-13-induced expression of the genes encoding IL-33, (a Th2-inducing cytokine 45-46 ), AMCase (capable of enhancing allergen-driven IL-13 production 47-48 ), and Fizz1 (capable of inducing airway eosinophilia and airway remodeling 49 ). We also see reduced IL-13-driven expression of Sprr2b following IL-12 treatment.…”

Section: Discussionmentioning

confidence: 99%

PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production

et al. 2013

View full text Add to dashboard Cite

Studies examining the role of PD-L2/PD-1 in asthma have yielded conflicting results. To clarify its role, we examined PD-L2 expression in biopsies from human asthmatics and lungs of aeroallergen-treated mice. PD-L2 expression in bronchial biopsies correlated with the severity of asthma. In mice, allergen exposure increased PD-L2 expression on pulmonary myeloid dendritic cells, and PD-L2 blockade diminished allergen-induced airway hyperresponsiveness (AHR). In contrast, PD-1 blockade had no impact, suggesting that PD-L2 promotes AHR in a PD-1-independent manner. Decreased AHR was associated with enhanced serum IL-12 p40 and in vitro stimulation of DCs with allergen and PD-L2-Fc reduced IL-12 p70 production, suggesting that PD-L2 inhibits allergen-driven IL-12 production. In our model, IL-12 did not diminish Th2 responses, but rather directly antagonized IL-13-inducible gene expression, highlighting a novel role for IL-12 in regulation of IL-13 signaling. Thus, allergen-driven enhancement of PD-L2 signaling through a PD-1-independent mechanism limits IL-12 secretion, exacerbating AHR.

show abstract

Section: Discussionmentioning

confidence: 99%

PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production

et al. 2013

View full text Add to dashboard Cite

show abstract

“…For example, CC10 and SP-D secreted by Clara cells play a protective role in asthma by inhibiting Th2 responses [10,30]. Pro-inflammatory mediators, such as acidic mammalian chitinase, are upregulated in Clara cells during Th2 inflammation and their inhibition ameliorates inflammation [31]. Chemokines, such as keratinocyte chemoattractant and macrophage inflammatory protein-1a, are secreted by Clara cells and their release following lipopolysaccharide application upon Clara cell ablation has been found to be significantly reduced [7].…”

Section: Discussionmentioning

confidence: 99%

Clara cells drive eosinophil accumulation in allergic asthma

Sonar

Ehmke²,

Marsh³

et al. 2011

Eur Respir J

View full text Add to dashboard Cite

Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the ''immunomodulatory barrier'' of the airway epithelium.To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 mg endotoxin-free ovalbumin in conjunction with naphthaleneinduced Clara cell depletion.Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung.These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.

show abstract

“…Blocking of acidic mammalian chitinase (expressed in lung epithelial cells and alveolar macrophages) by RNA interference improved allergic airway inflammation and hyperresponsiveness in a murine model [44].…”

Section: Targeting Kinasesmentioning

confidence: 99%