Berberine reduce allergic inflammation in a house dust mite allergic rhinitis mouse model

AbstractRegulation of epithelial cell death has emerged as a key mechanism controlling immune homeostasis in barrier surfaces. Necroptosis is a type of regulated necrotic cell death induced by receptor interacting protein kinase 3 (RIPK3) that has been shown to cause inflammatory pathologies in different tissues. The role of regulated cell death and particularly necroptosis in lung homeostasis and disease remains poorly understood. Here we show that mice with Airway Epithelial Cell (AEC)-specific deficiency of Fas-associated with death domain (FADD), an adapter essential for caspase-8 activation, developed exacerbated allergic airway inflammation in a mouse model of asthma induced by sensitization and challenge with house dust mite (HDM) extracts. Genetic inhibition of RIPK1 kinase activity by crossing to mice expressing kinase inactive RIPK1 as well as RIPK3 or MLKL deficiency prevented the development of exaggerated HDM-induced asthma pathology in FADDAEC-KO mice, suggesting that necroptosis of FADD-deficient AECs augmented the allergic immune response. These results reveal a role of AEC necroptosis in amplifying airway allergic inflammation and suggest that necroptosis could contribute to asthma exacerbations caused by respiratory virus infections inducing AEC death.

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Deficiency of CARS2, a principal cysteine persulfide synthase, aggravated house dust mite-induced allergic inflammation in a mouse model of asthma

10.1183/13993003.congress-2020.310 ◽

2020 ◽

Author(s):

Yusaku Sasaki ◽

Mituhiro Yamada ◽

Tadahisa Numakura ◽

Tomoaki Ida ◽

Masanobu Morita ◽

...

Keyword(s):

Mouse Model ◽

House Dust ◽

House Dust Mite ◽

Allergic Inflammation ◽

Dust Mite

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IL-25 Could Be Involved in the Development of Allergic Rhinitis Sensitized to House Dust Mite

Mediators of Inflammation ◽

10.1155/2017/3908049 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Dae Woo Kim ◽

Dong-Kyu Kim ◽

Kyoung Mi Eun ◽

Jun-Sang Bae ◽

Young-Jun Chung ◽

...

Keyword(s):

Allergic Rhinitis ◽

House Dust ◽

House Dust Mite ◽

Allergic Inflammation ◽

In Vitro Study ◽

High Dose ◽

Human Nasal Epithelial Cells ◽

Dust Mite

Background and Purpose. When house dust mite (HDM), a common allergen, comes into the mucosal membrane, it may stimulate innate immunity. However, the precise role of interleukin- (IL-) 25 in the development of HDM-induced nasal allergic inflammation is still unclear. Therefore, we investigated the role of IL-25 in allergic rhinitis (AR) patients sensitized to HDM. Methods. To confirm the production of IL-25 in human nasal epithelial cells (HNECs), we stimulated HNECs. IL-25 expression in the nasal mucosa from control, non-AR (NAR) patients, and HDM-sensitized AR patients was assessed using immunohistochemistry, and quantitative reverse transcription PCR. Correlations between IL-25 and other inflammatory markers were explored. Results. An in vitro study showed significantly elevated concentrations of IL-25 in the HNEC samples with highest doses of HDM. Nasal tissues from AR patients sensitized to HDM showed significantly higher IL-25 expression, compared to those from the control or NAR patients. Moreover, the expression of IL-25 in nasal tissues from AR patients sensitized to HDM was positively associated with Th2 markers, such as ECP and GATA3. Conclusions. IL-25 expression increased with high-dose HDM stimulation and was related to Th2 markers. Therefore, IL-25 neutralization might offer a new strategy for treating patients with HDM-sensitized AR.

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