Thymic Stromal Lymphopoietin Signaling Pathway Inhibition Attenuates Airway Inflammation and Remodeling in Rats with Asthma

Cheng, Zhe; Xi, Wang; Dai, Lingling; Jia, Liting; Jing, Xiaogang; Liu, Ying; Wang, Huan; Li, Pengfei; An, L.; Li, Meng

doi:10.1159/000490865

Cited by 19 publications

(13 citation statements)

References 31 publications

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“…Asthma is increasing in prevalence, with substantial morbidity [5,12,41,42]. The etiology of asthma involves inflammation, remodeling and AHR with an important role for ASM [5,9,10,12,[43][44][45][46][47]. Evidence from clinical studies suggest sex differences in the prevalence of asthma, and a potential role of sex steroids in the pathophysiology [4][5][6][48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor-Mediated Regulation of Intracellular Calcium in Human Airway Smooth Muscle Cells

Kalidhindi

Katragadda

Beauchamp

et al. 2019

Cell Physiol Biochem

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Background/Aims: With the prevalence of asthma being greater in women, detrimental effects of female sex steroids have been explored, but potential protective effects of androgens are not established. Airway smooth muscle (ASM) is a key cell type in contractility and remodelling of asthma. There are no data on expression and functionality of androgen receptor (AR) in human ASM cells. Methods: We used primary human ASM cells from non-asthmatics vs. asthmatics to determine AR expression at baseline and with inflammation measured using Western blotting/qRT-PCR, and the role of AR in regulating intracellular Ca2+ ([Ca2+]i) measured using Fluo-3 loaded real time [Ca2+]i imaging. Results: We found that compared to females, baseline AR is greater in male ASM and increases with inflammation/asthma. Androgens, via AR, blunted TNFα or IL-13-induced enhancement of ASM [Ca2+]i in both males and females, with retained efficacy in asthmatics. AR effects involve reduced Ca2+ influx via L-type channels and store-operated Ca2+ entry, the latter by downregulating STIM1 and Orai1 and increasing TMEM66. Conclusion: Our data show AR expression is increased in female ASM with asthma, but has retained functionality that could be used to reduce [Ca2+]i towards alleviating airway hyperresponsiveness.

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Section: Discussionmentioning

confidence: 99%

Androgen Receptor-Mediated Regulation of Intracellular Calcium in Human Airway Smooth Muscle Cells

Kalidhindi

Katragadda

Beauchamp

et al. 2019

Cell Physiol Biochem

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“…Epithelium‐generated cytokine TSLP was known as the master switch of initiating and maintaining allergic asthma . We have previously demonstrated that production of TSLP was increased in the lung of asthmatic mice and TSLP level is associated with DC maturation and the extension of Th2‐biased inflammation .…”

Section: Discussionmentioning

confidence: 99%

IL‐37 alleviates house dust mite‐induced chronic allergic asthma by targeting TSLP through the NF‐κB and ERK1/2 signaling pathways

et al. 2019

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Interleukin (IL)-37 has been described as a negative regulator of immune responses and is critical for asthma pathogenesis, but the mechanisms behind the protective role of IL-37 against allergic asthma are less well understood. We show here that IL-37 administered intranasally inhibited house dust mite (HDM)-induced chronic airway eosinophilic inflammation, goblet cell hyperplasia, peribronchial collagen deposition and airway hyperresponsiveness (AHR) to methacholine. In contrast to a weakened Th2 response in the lung that was characterized by the downregulation of Th2-associated cytokines and chemokines in IL-37-treated mice, IL-37 has no effect on relevant markers of systemic Th2 immune including serum immunoglobulins expression and in vitro production of Th2-associated cytokines by splenocytes on HDM recall. We demonstrated that the production of thymic stromal lymphopoietin (TSLP) in the lung tissue was associated with IL-37. Importantly, compared with IL-37 alone, TSLP coadministration with IL-37 restored HDM-induced airway inflammation and structural alterations, increased AHR to methacholine and promoted Th2-associated cytokine production. We further found that IL-37 inhibited the induction of TSLP expression by the main antigen of house dust mite, Der p1, by suppressing NF-jB and extracellular signal regulated kinase 1/2 (ERK1/2) activation in human bronchial epithelial (16-HBE) cells in vitro. These data highlight the importance of TSLP in IL-37-mediated protective role in asthma. IL-37 might represent a useful innovative and alternative therapy to control TSLP production in the airway.

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“…Asthma is a chronic inflammation of the airways characterized by the infiltration of inflammatory cells, inflammation, hyperresponsiveness and remodeling ( Murdoch and Lloyd, 2010) that can be induced or exacerbated by exposure to environmental triggers (Hardy et al, 2015). Its symptoms include excessive production of mucus leading to airway obstruction (Doeing and Solway, 2013) and is often accompanied by infiltration of the airways by eosinophils, mast cells and lymphocytes, thickening of the bronchial walls, and hypertrophy/hyperplasia of airway smooth muscle (Cheng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties

Gandhi

Vasconcelos

Haran³

et al. 2020

Phytomedicine

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Background: Asthma, the main inflammatory chronic condition affecting the respiratory system, is characterized by hyperresponsiveness and reversible airway obstruction, recruitment of inflammatory cells and excessive production of mucus. Cytokines as biochemical messengers of immune cells, play an important role in the regulation of allergic inflammatory and infectious airway processes. Essential oils of plant origin are complex mixtures of volatile and semi volatile organic compounds that determine the specific aroma of plants and are categorized by their biological activities.Purpose: We reviewed whether essential oils and their bioactive compounds of plant origin could modulate cytokines' immune responses and improve asthma therapy in experimental systems in vitro and in vivo.Methods: Electronic and manual search of articles in English available from inception up to November 2018 reporting the immunomodulatory activity of essential oils and their bioactive compounds for the management of asthma. We used PubMed, EMBASE, Scopus and Web of Science. Publications reporting preclinical experiments where cytokines were examined to evaluate the consequence of anti-asthmatic therapy were included.Results: 914 publications were identified and 13 were included in the systematic review.Four articles described the role of essential oils and their bioactive compounds on bronchial asthma using cell lines; nine in vivo studies evaluated the anti-inflammatory efficacy and immunomodulating effects of essential oil and their secondary metabolites on cytokines production and inflammatory responses. The most important immunopharmacological mechanisms reported were the regulation of cytokine

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Thymic Stromal Lymphopoietin Signaling Pathway Inhibition Attenuates Airway Inflammation and Remodeling in Rats with Asthma

Cited by 19 publications

References 31 publications

Androgen Receptor-Mediated Regulation of Intracellular Calcium in Human Airway Smooth Muscle Cells

Androgen Receptor-Mediated Regulation of Intracellular Calcium in Human Airway Smooth Muscle Cells

IL‐37 alleviates house dust mite‐induced chronic allergic asthma by targeting TSLP through the NF‐κB and ERK1/2 signaling pathways

Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties

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