Immunologic mechanisms in asthma

Boonpiyathad, Tadech; Sözener, Zeynep Çelebi; Satitsuksanoa, Pattraporn; Akdiş, Cezmi A.

doi:10.1016/j.smim.2019.101333

Cited by 353 publications

(261 citation statements)

References 131 publications

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“…The term "asthma" is recognized as a diagnosis that combines several endotypes and various phenotypes, each of which being manifested by wheezing, coughing, shortness of breath, chest tightness, decreased expiratory airflow, hyperreactivity, airway remodeling, and mucus hyperproduction [16]. It is known that even within the same endotype, patients may have both different degrees of disease severity and a response to the treatment [17]. Phenotypes of the disease can also change with time [18].…”

Section: Asthmamentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferatoractivated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

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Section: Asthmamentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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“…As EGFR protein levels are increased in severe asthma, 54 asthma. 61 However, induction of IL-13 mRNA and protein has also been observed in wounded bronchial epithelial cells in vitro, 62 and in our own unpublished work, we also have observed a significant increase in IL-13 protein release from primary bronchial epithelial cells in response to challenge with double-stranded RNA (data not shown). In the published work, release of IL-13 following wounding was shown to enhance epithelial repair via HB-EGF.…”

Section: Discussionmentioning

confidence: 51%

Involvement of the epidermal growth factor receptor in IL‐13–mediated corticosteroid‐resistant airway inflammation

Davies

Perotin-Collard

Kelly

et al. 2020

Clin Experimental Allergy

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Background: Effective treatment for severe asthma is a significant unmet need. While eosinophilic inflammation caused by Type 2 cytokines is responsive to corticosteroid and biologic therapies, many severe asthmatics exhibit corticosteroid-unresponsive mixed granulocytic inflammation.Objective: Here, we tested the hypothesis that the pro-allergic cytokine, IL-13, can drive both corticosteroid-sensitive and corticosteroid-resistant responses.Results: By integration of in vivo and in vitro models of IL-13-driven inflammation, we identify a role for the epidermal growth factor receptor (EGFR/ERBB1) as a mediator of corticosteroid-unresponsive inflammation and bronchial hyperresponsiveness driven by IL-13. Topological data analysis using human epithelial transcriptomic data from the U-BIOPRED cohort identified severe asthma groups with features consistent with the presence of IL-13 and EGFR/ERBB activation, with involvement of distinct EGFR ligands. Our data suggest that IL-13 may play a dual role in severe asthma: on the one hand driving pathologic corticosteroid-refractory mixed granulocytic inflammation, but on the other hand underpinning beneficial epithelial repair responses, which may confound responses in clinical trials. Conclusion and ClinicalRelevance: Detailed dissection of those molecular pathways that are downstream of IL-13 and utilize the ERBB receptor and ligand family to drive corticosteroid-refractory inflammation should enhance the development of new treatments that target this sub-phenotype(s) of severe asthma, where there is an unmet need. K E Y W O R D S animal models, asthma, basic mechanisms, corticosteroid-refractory, epithelium, neutrophils | 673 DAVIES Et Al.

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“…Asthma includes many clinical presentations with different types of excessive immunological responses [2,3] which involve many immune cells and broblasts and epithelial cells [26]. Activation of airway epithelial cells and release of cytokines including IL-25, IL-33, and TSLP play a major role in onset of asthma [27]. IL-25 and IL-33 from activated airway epithelial cells and other sources induce the expansion and activation of ILC2s which produce type II in ammatory cytokines [8,11,26,27].…”

Section: Discussionmentioning

confidence: 99%

“…Activation of airway epithelial cells and release of cytokines including IL-25, IL-33, and TSLP play a major role in onset of asthma [27]. IL-25 and IL-33 from activated airway epithelial cells and other sources induce the expansion and activation of ILC2s which produce type II in ammatory cytokines [8,11,26,27]. The current study elucidated that molecular hydrogen inhibited IL-33 expression in HDM activated human bronchial epithelial cells (16HBE) at transcriptional level and might also at post-transcription level.…”

Section: Discussionmentioning

confidence: 99%

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis

Zhang¹,

Feng

Fan

et al. 2020

Preprint

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Background: Asthma is one of the most common noninfectious chronic diseases characterized by type II inflammation. This study aimed to investigate the effects of molecular hydrogen on the pathogenesis of asthma.Methods: OVA sensitized asthma mouse model was established and hydrogen/oxygen mixture was used to treat asthmatic mice. Serum and BALF cytokines were measured with specific ELISA assays. E-cadherin and ZO-1 were detected by immunohistochemical staining and expression of caspase 3 and 9, NF-kB, IL-33 and ST2 was assessed by quantitative real-time PCR, western blot and / or immunofluorescence. IL-33 promoter activity was analyzed by dual-luciferase assay. ILC2 population was assayed by flow cytometry and differentially expressed miRNAs were detected using miRNA array. Results: Serum and BALF levels of IL-33 and other alarmin and type II cytokines were greatly increased by OVA and inhibited by H2 in asthmatic mice. The expression of NF-kB (p65) and ST2 was upregulated by OVA and suppressed by H2. ILC2 population was markedly increased in OVA-induced asthmatic mice, and such increase was inhibited by H2. E-cadherin and ZO-1 levels in airway tissues of asthmatic mice were significantly lower than that of control mice, and the reduction was recovered by H2 treatment. H2 alleviated HDM induced apoptosis of 16HBE cells, upregulation of IL-33 and ST2, and elevation of IL-33 promoter activity. A group of miRNAs differentially expressed in HDM and HDM+H2 treated 16HBE cells were identified. Conclusions: These data demonstrated that H2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutic method for asthma and other conditions of type II inflammation.

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Immunologic mechanisms in asthma

Cited by 353 publications

References 131 publications

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Involvement of the epidermal growth factor receptor in IL‐13–mediated corticosteroid‐resistant airway inflammation

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis

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Immunologic mechanisms in asthma

Cited by 353 publications

References 131 publications

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Involvement of the epidermal growth factor receptor in IL‐13–mediated corticosteroid‐resistant airway inflammation

Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2&nbsp;Axis

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Molecular Hydrogen Alleviates Asthma Through Inhibiting IL-33/ILC2 Axis