IL‐17A increases TNF‐α‐induced COX‐2 protein stability and augments PGE<sub>2</sub> secretion from airway smooth muscle cells: impact on β<sub>2</sub>‐adrenergic receptor desensitization

Rumzhum, Nowshin N.; Patel, Brijeshkumar S.; Prabhala, Pavan; Gelissen, Ingrid C.; Oliver, Brian G.; Ammit, Alaina J.

doi:10.1111/all.12810

Cited by 18 publications

(20 citation statements)

References 39 publications

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“…Our further mediation analyses indicated that IL‐1β and TNF‐α, as two pro‐inflammatory cytokines, could play key roles in depressive symptom‐associated impaired BDR and neutrophilic airway inflammation. IL‐1β and TNF‐α were associated with decreased glucocorticoid expression along with impaired nuclear translocation, glucocorticoid receptor phosphorylation and β 2 ‐adrenergic desensitization . Therefore, these results suggest that depressive symptom‐associated activation of systemic M 1 macrophages could produce an over‐expression of pro‐inflammatory cytokines and promote T H 1 differentiation.…”

Section: Discussionmentioning

confidence: 84%

Depressive symptom‐associated IL‐1β and TNF‐α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma

Zhang

Zheng

et al. 2019

Clin Experimental Allergy

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Background: Depressive symptoms worsen asthma outcomes; however, the mechanism remains largely unexplored.Objective: This study aimed to determine whether depressive symptom-associated immune inflammation correlates with impaired bronchodilator response (BDR) and airway inflammatory phenotypes.Methods: Eligible adults with asthma (n = 198) underwent clinical assessment, sputum induction and blood sampling. Depressive symptoms were defined by scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D).Pre-and post-bronchodilator spirometry was performed for BDR. Airway inflammatory phenotypes were defined by sputum cell counts. CRP, IL-1β, IL-5, IL-6, IL-8, TNF-α, IFN-γ, CCL17 and CCL22 in serum and sputum were detected.Results: Compared with the non-depressive group (n = 174), the depressive group (n = 24) exhibited impaired BDR (P = 0.032) and increased sputum neutrophils (P = 0.023), which correlated with the HADS-D scores (P = 0.027 and P = 0.029).Levels of IL-1β, TNF-α and IFN-γ in the serum and those of IL-1β and IFN-γ in the sputum were elevated in the depressive group compared to those in the non-depressive group (all P < 0.05). Multiple regression models indicated that TNF-α in the

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Section: Discussionmentioning

confidence: 84%

Depressive symptom‐associated IL‐1β and TNF‐α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma

Zhang

Zheng

et al. 2019

Clin Experimental Allergy

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“…As we have previously shown, PGE 2 induces heterologous desensitization of the β 2 -adrenergic receptor (Alkhouri et al, 2014;Rumzhum, Patel, et al, 2016, thus we hypothesized that EP 2 or EP 4 receptors may be involved in regulating β 2 -adrenergic receptor function in ASM cells. In accordance with our previous publication (Alkhouri et al, 2014), PGE 2 -induced tachyphylaxis to short-(salbutamol) or long-(formoterol) β 2 -agonists (measured by cAMP release).…”

Section: Pge 2 Does Not Induce Ep 2 or Ep 4 Receptor Mrna Expressionmentioning

confidence: 87%

EP₂ and EP₄ receptor antagonists: Impact on cytokine production and β₂‐adrenergic receptor desensitization in human airway smooth muscle

Bradbury

Rumzhum

Ammit

2018

Journal Cellular Physiology

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Prostaglandin E2 (PGE2) is a key prostanoid known to have both proinflammatory and anti‐inflammatory impact in the context of chronic respiratory diseases. We hypothesize that these opposing effects may be the result of different prostanoid E (EP) receptor‐mediated signaling pathways. In this study, we focus on two of the four EP receptors, EP2 and EP4, as they are known to induce cyclic adenosine monophosphate (cAMP)‐dependent signaling pathways. Using primary human airway smooth muscle (ASM) cells, we first focussed on the PGE2‐induced production of two cAMP‐dependent proinflammatory mediators: interleukin 6 (IL‐6) and cyclo‐oxygenase 2 production. We show that PGE2‐induced IL‐6 protein secretion occurs via an EP2‐mediated pathway, in a manner independent of receptor‐mediated effects on messenger RNA (mRNA) expression and temporal activation kinetics of the transcription factor cAMP response element binding. Moreover, stimulation of ASM with PGE2 did not establish a positive, receptor‐mediated, feedback loop, as mRNA expression for EP2 and EP4 receptors were not upregulated and receptor antagonists were without effect. Our studies revealed that the EP2, but not the EP4, receptor is responsible for β2‐adrenergic desensitization induced by PGE2. We demonstrate that PGE2‐induced heterologous receptor desensitization responsible for tachyphylaxis to short‐ (salbutamol) or long‐ (formoterol) β2‐agonists (measured by cAMP release) can be reversed by the EP2 receptor antagonist PF‐04418948. Importantly, this study highlights that inhibiting the EP2 receptor restores β2‐adrenergic receptor function in vitro and offers an attractive novel therapeutic target for treating infectious exacerbations in people suffering from chronic respiratory diseases in the future.

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“…The expression of COX-2 is induced at the site of inflammation in response to inflammatory stimuli, such as IL-1β, TNF-α, TGF-β 46,47 . Our results indicated that TGF-β1 NAb signficantly reduced COX-2 expression in HCT-116 cells exposed to the CMs of THP-1 macrophages.…”

Section: Discussionmentioning

confidence: 99%

Response gene to complement 32 expression in macrophages augments paracrine stimulation-mediated colon cancer progression

et al. 2019

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M2-polarized tumor associated macrophages (TAMs) play an important role in tumor progression. It has been reported that response gene to complement 32 (RGC-32) promotes M2 macrophage polarization. However, whether RGC-32 expression in macrophages could play a potential role in tumor progression remain unclear. Here we identified that increasing RGC-32 expression in colon cancer and tumor associated macrophages was positively correlated with cancer progression. In vitro studies confirmed that colon cancer cells upregulated RGC-32 expression of macrophages via secreting TGF-β1. RGC-32 expression promoted macrophage migration. In addition, stimulation of HCT-116 cells with the condition mediums of RGC-32-silienced or over-expressed macrophages affected tumor cell colony formation and migration via altered COX-2 expression. In an animal model, macrophages with RGC-32 knockdown significantly decreased the expression of COX-2 and Ki67 in the xenografts, and partly inhibited tumor growth. Together, our results provide the evidences for a critical role of TGF-β1/RGC-32 pathway in TAMs and colon cancer cells during tumor progression.

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IL‐17A increases TNF‐α‐induced COX‐2 protein stability and augments PGE₂ secretion from airway smooth muscle cells: impact on β₂‐adrenergic receptor desensitization

Abstract: As PGE2 is a multifunctional prostanoid with diverse roles in respiratory disease, our studies demonstrate a novel function for IL-17A in airway inflammation by showing for the first time that IL-17A impacts on the COX-2/PGE2 pathway, molecules known to contribute to disease exacerbation.

Cited by 18 publications

References 39 publications

Depressive symptom‐associated IL‐1β and TNF‐α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma

Depressive symptom‐associated IL‐1β and TNF‐α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma

EP₂ and EP₄ receptor antagonists: Impact on cytokine production and β₂‐adrenergic receptor desensitization in human airway smooth muscle

Response gene to complement 32 expression in macrophages augments paracrine stimulation-mediated colon cancer progression

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IL‐17A increases TNF‐α‐induced COX‐2 protein stability and augments PGE2 secretion from airway smooth muscle cells: impact on β2‐adrenergic receptor desensitization

Abstract: As PGE2 is a multifunctional prostanoid with diverse roles in respiratory disease, our studies demonstrate a novel function for IL-17A in airway inflammation by showing for the first time that IL-17A impacts on the COX-2/PGE2 pathway, molecules known to contribute to disease exacerbation.

Cited by 18 publications

References 39 publications

Depressive symptom‐associated IL‐1β and TNF‐α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma

Depressive symptom‐associated IL‐1β and TNF‐α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma

EP2 and EP4 receptor antagonists: Impact on cytokine production and β2‐adrenergic receptor desensitization in human airway smooth muscle

Response gene to complement 32 expression in macrophages augments paracrine stimulation-mediated colon cancer progression

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IL‐17A increases TNF‐α‐induced COX‐2 protein stability and augments PGE₂ secretion from airway smooth muscle cells: impact on β₂‐adrenergic receptor desensitization

EP₂ and EP₄ receptor antagonists: Impact on cytokine production and β₂‐adrenergic receptor desensitization in human airway smooth muscle