Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

Stenberg, Henning; Wadelius, Erik; Moitra, Subhabrata; Åberg, Ida; Ankerst, Jaro; Diamant, Zuzana; Bjermer, Leif; Tufvesson, Ellen

doi:10.1080/1354750x.2017.1375559

“…It was of interest to note that serum CC16 levels of asthmatic mice were signi cantly increased upon the rst HDM challenge compared to baseline, yet maximally declined to a very low extent one week after the last HDM challenge. These ndings were similar to those of a recent study that serum CC16 concentrations were rapidly elevated in asthmatic subjects at 1h postallergen challenge [34]. It can be assumed that transient augmentation of serum CC16 following acute HDM challenge is mainly due to allergen-induced increased permeability and diffusion from the epithelial lining uid into the circulation.…”

Section: Discussionsupporting

confidence: 90%

Clara cell 16KDa protein mitigates house dust mite-induced airway inflammation and damage via regulating airway epithelial cell apoptosis in a manner dependent on HMGB1-mediated signaling inhibition.

Liu

¹

,

Lu

²

,

Zhang

³

et al. 2021

Preprint

0

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Background: House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. High mobility group box 1 (HMGB1) is critically required for cellular damage and apoptosis as an important endogenous danger signal. Recently, Clara cell 16KDa protein (CC16) has been identified to exert anti-inflammatory and immunomodulatory influence in various injury-related diseases model. However, little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16.Methods: Mice were sensitized and challenged by HDM extract and administrated intranasally with CC16 (5ug/g or 10ug/g) or saline in the challenged period. The BEAS-2B human airway epithelial cell line were cultured with CC16 or the control vehicle and then exposed to HDM. Knockdown or overexpression of HMGB1 was induced by cell transfection or intratracheal injection of recombinant adenovirus.Results: CC16 treatment decreased airway inflammation and histological damage of airway epithelium dose-dependently in HDM-induced asthma model. Airway epithelia apoptosis upon HDM stimulation was noticeably abrogated by CC16 in vivo and in vitro. In addition, upregulation of HMGB1 expression and its related signaling were also detected under HDM conditions, while silencing HMGB1 significantly inhibited the apoptosis of BEAS-2B cells. Furthermore, the activity of HMGB1-mediated signaling was restrained after CC16 treatment whereas HMGB1 overexpression abolished the protective effect of CC16 on HDM-induced airway epithelia apoptosis.Conclusions: Our data confirm that CC16 attenuates HDM-mediated airway inflammation and damage via suppressing airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting the role of CC16 as a potential protective option for HDM-induced asthma.

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“…It was of interest to note that serum CC16 levels of asthmatic mice were signi cantly increased upon the rst HDM challenge compared to baseline, yet maximally declined to a very low extent one week after the last HDM challenge. These ndings were similar to those of a recent study that serum CC16 concentrations were rapidly elevated in asthmatic subjects at 1h post-allergen challenge [34]. It can be assumed that transient augmentation of serum CC16 following acute HDM challenge is mainly due to allergen-induced increased permeability and diffusion from the epithelial lining uid into the circulation.…”

Section: Discussionsupporting

confidence: 90%

Clara cell 16KDa protein mitigates house dust mite-induced airway inflammation and damage via regulating airway epithelial cell apoptosis in a manner dependent on HMGB1-mediated signaling inhibition.

Liu

¹

,

Lu

²

,

Zhang

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Background: House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. High mobility group box 1 (HMGB1) is critically required for cellular damage and apoptosis as an important endogenous danger signal. Recently, Clara cell 16KDa protein (CC16) has been identified to exert anti-inflammatory and immunomodulatory influence in various injury-related diseases model. However, little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16.Methods: Mice were sensitized and challenged by HDM extract and administrated intranasally with CC16 (5ug/g or 10ug/g) or saline in the challenged period. The BEAS-2B human airway epithelial cell line were cultured with CC16 or the control vehicle and then exposed to HDM. Knockdown or overexpression of HMGB1 was induced by cell transfection or intratracheal injection of recombinant adenovirus.Results: CC16 treatment decreased airway inflammation and histological damage of airway epithelium dose-dependently in HDM-induced asthma model. Airway epithelia apoptosis upon HDM stimulation was noticeably abrogated by CC16 in vivo and in vitro. In addition, upregulation of HMGB1 expression and its related signaling were also detected under HDM conditions, while silencing HMGB1 significantly inhibited the apoptosis of BEAS-2B cells. Furthermore, the activity of HMGB1-mediated signaling was restrained after CC16 treatment whereas HMGB1 overexpression abolished the protective effect of CC16 on HDM-induced airway epithelia apoptosis.Conclusions: Our data confirm that CC16 attenuates HDM-mediated airway inflammation and damage via suppressing airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting the role of CC16 as a potential protective option for HDM-induced asthma.

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“…A recent study additionally demonstrated a puzzling dichotomy: CC16 levels were increased in plasma but reduced in urine after allergen challenge in asthmatic patients. 97 Bronchial surface levels of surfactant protein D in patients with severe asthma can be both increased and decreased, 98,99 questioning its value as a permeability probe. Unsurprisingly, replacement of these indirect indices with direct noninvasive markers of airway absorption permeability has been strongly recommended.…”

Section: Airway Plasma Exudation and Absorption In Patients With Asthmentioning

confidence: 99%

Airways exudation of plasma macromolecules: Innate defense, epithelial regeneration, and asthma

Persson

¹

2019

Journal of Allergy and Clinical Immunology

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This review discusses in vivo airway aspects of plasma exudation in relation to current views on epithelial permeability and epithelial regeneration in health and disease. Microvascular-epithelial exudation of bulk plasma proteins characteristically occurs in asthmatic patients, being especially pronounced in those with severe and exacerbating asthma. Healthy human and guinea pig airways challenged by noninjurious histamine-leukotriene-type autacoids also respond through prompt mucosal exudation of nonsieved plasma macromolecules. Contrary to current beliefs, epithelial permeability in the opposite direction (ie, absorption of inhaled molecules) has not been increased in patients with asthma and allergic rhinitis or in acutely exuding healthy airways. A slightly increased subepithelial hydrostatic pressure produces such unidirectional outward perviousness to macromolecules. Lack of increased absorption permeability in asthmatic patients can further be reconciled with occurrence of epithelial shedding, leaving small patches of denuded basement membrane. Counteracting escalating barrier breaks, plasma exudation promptly covers the denuded patches. Here it creates and sustains a biologically active barrier involving a neutrophil-rich, fibrin-fibronectin net. Furthermore, in the plasma-derived milieu, all epithelial cell types bordering the denuded patch dedifferentiate and migrate from all sides to cover the denuded basement membrane. However, this speedy epithelial regeneration can come at a cost. Guinea pig in vivo studies demonstrate that patches of epithelial denudation regeneration are exudation hot spots evoking asthma-like features, including recruitment/activation of granulocytes, proliferation of fibrocytes/smooth muscle cells, and basement membrane thickening. In conclusion, nonsieved plasma macromolecules can operate on the intact airway mucosa as potent components of first-line innate immunity responses. Exuded plasma also takes center stage in epithelial regeneration. When exaggerated, epithelial regeneration can contribute to the inception and development of asthma.

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Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

Cited by 23 publications

References 40 publications

Clara cell 16KDa protein mitigates house dust mite-induced airway inflammation and damage via regulating airway epithelial cell apoptosis in a manner dependent on HMGB1-mediated signaling inhibition.

Clara cell 16KDa protein mitigates house dust mite-induced airway inflammation and damage via regulating airway epithelial cell apoptosis in a manner dependent on HMGB1-mediated signaling inhibition.

Clara cell 16KDa protein mitigates house dust mite-induced airway inflammation and damage via regulating airway epithelial cell apoptosis in a manner dependent on HMGB1-mediated signaling inhibition.

Airways exudation of plasma macromolecules: Innate defense, epithelial regeneration, and asthma

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