Inflammatory and contractile profile in LPS-challenged equine isolated bronchi: Evidence for IL-6 as a potential target against AHR in equine asthma

Calzetta, Luigino; Pistocchini, Elena; Cito, Giuseppe; Ritondo, Beatrice Ludovica; Verri, Stefano; Rogliani, Paola

doi:10.1016/j.pupt.2022.102125

Cited by 6 publications

(4 citation statements)

References 71 publications

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“…Interestingly, we did not see any major effects of IL-8 levels, which was inhibited, albeit minimally, in previous studies utilizing an LPS-induced inflammatory response in porcine epithelial cells [59]. While capsaicin has been shown to inhibit MCP-1 levels in macrophages through TRPV1 activation [61,62], these effects are not seen here in our study or other studies investigating the inflammatory responses of epithelial cells [63].…”

Section: Discussioncontrasting

confidence: 70%

Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue

Robinson,

Li,

Wang

et al. 2023

Life

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Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key inflammatory pathways, mitigate the pathological effects of inflammation, and offer new avenues for therapeutic interventions in IBD. This study investigates the anti-inflammatory effects of 5-HT2A ligands, including psilocybin, 4-AcO-DMT, and ketanserin, in combination with TRP channel ligands, including capsaicin, curcumin, and eugenol, on the inflammatory response induced by tumor necrosis factor (TNF)-α and interferon (IFN)-γ in human 3D EpiIntestinal tissue. Enzyme-linked immunosorbent assay was used to assess the expression of pro-inflammatory markers TNF-α, IFN-γ, IL-6, IL-8, MCP-1, and GM-CSF. Our results show that psilocybin, 4-AcO-DMT, and eugenol significantly reduce TNF-α and IFN-γ levels, while capsaicin and curcumin decrease these markers to a lesser extent. Psilocybin effectively lowers IL-6 and IL-8 levels, but curcumin, capsaicin, and 4-AcO-DMT have limited effects on these markers. In addition, psilocybin can significantly decrease MCP-1 and GM-CSF levels. While ketanserin lowers IL-6 and GM-CSF levels, there are no effects seen on TNF-α, IFN-γ, IL-8, or MCP-1. Although synergistic effects between 5-HT2A and TRP channel ligands are minimal in this study, the results provide further evidence of the anti-inflammatory effects of psilocybin and eugenol. Further research is needed to understand the mechanisms of action and the feasibility of using these compounds as anti-inflammatory therapies for conditions like IBD.

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Section: Discussioncontrasting

confidence: 70%

Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue

Robinson,

Li,

Wang

et al. 2023

Life

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“…The consistent effect of BNT162b2 on both histaminergic and parasympathetic pathways suggests that the vaccine may both directly and indirectly increase AHR by acting on ASM, vagal fibers, and intramural ganglia [ 47 , 48 ]. Considering the effect on all the EFS frequencies investigated in this study, evidently BNT162b2 may have a facilitator activity on the release of contractile neurotrasmitters from all the parasympathetic post-ganglionic neurons, including the large and small myelinated A- and B-fibers, as well as the nonmyelinated C-fibers, the latter of which are involved in the acute neurogenic inflammation that is a detrimental condition in severe asthma [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma

et al. 2023

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The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

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“…The obtained CSE stock is then diluted 1:10 for the overnight treatment of bronchial tissue (van Rijt et al, 2012). CSE treatment increases cytokine expression and reduces nuclear expression of sirtuin and histone deacetylase (HDAC) (Calzetta, Pistocchini, Cito, Ritondo, et al, 2022c). CSE also induces mucus hypersecretion and mucin MUC5AC gene and protein overexpression (Cortijo et al, 2011;Di et al, 2012).…”

Section: Overnight Treatment With Csementioning

confidence: 99%

“…Although airway remodelling cannot be replicated in experiments with isolated airways, the main mechanics and inflammatory characteristics of PAL can be reproduced ex vivo in passively sensitised bronchi. During the sensitisation procedure, isolated airways can be incubated overnight also in the presence of CCh administered at low dose (i.e., 1 μM) in order to activate M receptors and, thus, mimic altered activity and plasticity of parasympathetic pathway as well as tissue inflammatory response (Calzetta, Pistocchini, Cito, Ritondo, et al, 2022c; Gosens et al, 2006; Kistemaker & Prakash, 2019; Rogliani, Ritondo, Zerillo, et al, 2021c). Of note, it has been demonstrated that the stimulation of M receptors with other iatrogenic agonists such as methacholine, elicited persistent ventilation defects due to obstruction in specific lung regions of asthmatic patients (de Lange et al, 2007).…”

Section: In Vitro Studies With Isolated Airwaysmentioning

confidence: 99%

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

Calzetta,

Page,

Matera

et al. 2023

British J Pharmacology

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Isolated airway smooth muscle has been extensively investigated since 1840 to understand the pharmacology of airway diseases. There has been often poor predictability from murine experiments to drugs evaluated in patients with asthma or chronic obstructive pulmonary disease (COPD). However, the use of isolated human airways represents a sensible strategy to optimise the development of innovative molecules for the treatment of respiratory diseases. This review aims to provide updated evidence on the current uses of isolated human airways in validated in vitro methods to investigate drugs in development for the treatment of chronic obstructive respiratory disorders. This review also provides historical notes on the pioneering pharmacological research on isolated human airway tissues, the key differences between human and animal airways, as well as the pivotal differences between human medium bronchi and small airways. Experiments carried out with isolated human bronchial tissues in vitro and ex vivo replicate many of the main anatomical, pathophysiological, mechanical and immunological characteristics of patients with asthma or COPD. In vitro models of asthma and COPD using isolated human airways can provide information that is directly translatable into humans with obstructive lung diseases. Regardless of the technique used to investigate drugs for the treatment of chronic obstructive respiratory disorders (i.e. isolated organ bath systems, videomicroscopy, wire myography), the most limiting factors to produce high‐quality and repeatable data remain closely tied to the manual skills of the researcher conducting experiments and the availability of suitable tissue.

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Inflammatory and contractile profile in LPS-challenged equine isolated bronchi: Evidence for IL-6 as a potential target against AHR in equine asthma

Cited by 6 publications

References 71 publications

Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue

Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

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