scholarly journals Ruxolitinib inhibits poly(I:C) and type 2 cytokines‐induced CCL5 production in bronchial epithelial cells: A potential therapeutic agent for severe eosinophilic asthma

2021 ◽  
Author(s):  
Mitsuru Sada ◽  
Masato Watanabe ◽  
Toshiya Inui ◽  
Keitaro Nakamoto ◽  
Aya Hirata ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Therapeutic Agent ◽  
Bronchial Epithelial Cells ◽  
Poly I:C ◽  
Eosinophilic Asthma ◽  
Bronchial Epithelial ◽  
Severe Eosinophilic Asthma ◽  
Potential Therapeutic Agent ◽  
Type 2 Cytokines

scholarly journals Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model

2017 ◽  
Vol 3 (4) ◽  
pp. 00047-2017 ◽  
Author(s):  
Mandy Menzel ◽  
Hamid Akbarshahi ◽  
Irma Mahmutovic Persson ◽  
Manoj Puthia ◽  
Leif Bjermer ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Asthma Exacerbation ◽  
Bronchial Epithelial Cells ◽  
Poly I:C ◽  
Bronchial Epithelial ◽  
Interleukin 33 ◽  
Caspase 1 ◽  
Inflammatory Parameters ◽  
Asthma Exacerbations

Rhinovirus infections are common triggers of asthma exacerbations. Viruses can activate the inflammasome, resulting in processing and activation of caspase-1. This recruitment triggers production of interleukin (IL)-1β and IL-18, which have been implicated in asthma. Elucidating the involvement of the inflammasome and its compartments, such as caspase-1, in asthma exacerbations is warranted.Gene expression of caspase-1 was measured in rhinovirus-infected primary bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection. In anin vivoexacerbation experiment C57BL/6 wild-type and caspase-1-/-mice were challenged with house dust mite followed by exposures to the viral mimic poly(I:C). General lung inflammatory parameters and levels of T-helper type 2 (Th2)-upstream cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 were assessed.Caspase-1 expression was elevated after rhinoviral infection exclusively in bronchial epithelial cells from asthmatics. In a translational mouse model of asthma exacerbation effects of caspase-1 on airway inflammation and Th2-upstream cytokines were explored. Caspase-1 deficient mice exhibited no alterations of general lung inflammatory parameters, but showed markedly reduced eosinophilia. Furthermore, the Th2-upstream cytokines IL-33, TSLP and IL-25 were reduced at exacerbation in mice lacking caspase-1.Rhinovirus infection increases bronchial epithelial caspase-1 in asthma. Caspase-1 may induce production of lung Th2-upstream cytokines and eosinophilia at exacerbations. Further targeting of caspase-1 signalling is warranted to explore its role in asthma exacerbations.

Exposure to Silica Crystals and Poly (I:C) Induces Caspase-Dependent Apoptosis of Human Bronchial Epithelial Cells

2013 ◽  
Vol 131 (2) ◽  
pp. AB198
Author(s):  
Hirotoshi Unno ◽  
Kyoko Futamura ◽  
Reiji Kojima ◽  
Hideaki Morita ◽  
Hirohisa Saito ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Poly I:C ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Silica Crystals

scholarly journals Periostin: contributor to abnormal airway epithelial function in asthma?

2020 ◽  
pp. 2001286 ◽  
Author(s):  
Janette K. Burgess ◽  
Marnix R. Jonker ◽  
Marijn Berg ◽  
Nick T. H. ten Hacken ◽  
Kerstin B. Meyer ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Healthy Controls ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Protein Levels ◽  
Mucin Genes ◽  
Asthma Patients ◽  
Bronchial Biopsies

Periostin may serve as a biomarker for type-2-mediated eosinophilic airway inflammation in asthma. We hypothesised that type-2 cytokine IL-13 induces airway epithelial expression of periostin, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on periostin expression in BEAS-2B and air-liquid interface (ALI)-differentiated primary bronchial epithelial cells (PBECs). Additionally, effects of recombinant human periostin on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. In bronchial biopsies and induced sputum from asthma patients and healthy controls, we analysed periostin single cell gene expression and protein levels.IL-13 increased POSTN expression in both cell types, which was accompanied by EMT-related features in BEAS-2B. In ALI-differentiated PBECs, IL-13 increased periostin basolateral and apical release. Apical administration of periostin increased the expression of MMP9, MUC5B and MUC5AC. In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus controls. Higher protein levels of periostin, expressed in epithelial and subepithelial layers, was confirmed in bronchial biopsies from asthma patients compared to healthy controls. Although sputum periostin levels were not higher in asthma, levels correlated with eosinophil numbers and coughing up mucus.Periostin expression is increased by IL-13 in bronchial epithelial cells and higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of periostin increased epithelial expression of mucin genes, supporting the relationship of periostin with type-2 mediated asthma and mucus secretion.

scholarly journals Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Monica Boita ◽  
Caterina Bucca ◽  
Giuseppe Riva ◽  
Enrico Heffler ◽  
Giovanni Rolla
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Cell Cultures ◽  
Nasal Polyps ◽  
Dermatophagoides Pteronyssinus ◽  
Poly I:C ◽  
Type 2 Cytokines ◽  
Sinus Mucosa

Background. T2 inflammation of chronic rhinosinusitis with nasal polyps (CRSwNP) may be influenced by epithelial cytokines release (TSLP, IL-25, and IL-33). We investigated the release of TSLP, IL-25, and IL-33 by epithelial CRSwNP cells compared to epithelial sinus mucosa cells of patients with chronic rhinosinusitis without nasal polyps (CRSsNP).Methods. IL-25, IL-33, and TSLP were measured by ELISA in the supernatant of cell cultures derived by CRSwNP (9 patients, 6 atopic) and CRSsNP (7 patients, 2 atopic) in baseline condition and following stimulation withDermatophagoides pteronyssinus(DP),Aspergillus fumigatus(AF), and poly(I:C).Results. CRSwNP epithelial cells released increased levels of IL-25 (from 0.12 ± 0.06 pg/ml to 0.27 ± 0.1 pg/ml,p<0.01) and TSLP (from 0.77 ± 0.5 pg/ml to 2.53 ± 1.17 pg/ml,p<0.001) following poly(I:C) stimulation, while CRSsNP epithelial cells released increased levels of IL-25 and IL-33 following AF and DP stimulation, respectively (IL-25: from 0.18 ± 0.07 pg/ml to 0.51 ± 0.1 pg/ml,p<0.001; IL-33: from 2.57 ± 1.3 pg/ml to 5.7 ± 3.1 pg/ml,p<0.001).Conclusions. CRSwNP epithelial cells release TSLP and IL-25 when stimulated by poly(I:C) but not by DP or AF, suggesting that viral infection may contribute to maintain and amplify the T2 immune response seen in CRSwNP.

Sign in / Sign up

Export Citation Format

Share Document