Inhibitory action of roxithromycin on histamine release and prostaglandin D2 production from β-defensin 2-stimulated mast cells

Kase, Kaori; Hua, Jian; Yokoi, Hidenori; Ikeda, Katsuhisa; Nagaoka, Isao

doi:10.3892/ijmm_00000136

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…Consistent data indicate that mechanisms underlying macrolides regulatory effects on the immune response, rely on the modulation of cell signaling pathways. Hence, modulation of Ca 2+ signal pathways has been suggested in neutrophils (Mitsuyama et al, 1997) and in rat mast cells (Kase et al, 2009). Interactions with MAPK signaling pathways have also been identified.…”

Section: Macrolides Influence On Cell Signalingmentioning

confidence: 99%

Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

et al. 2021

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Azithromycin (AZM) is a 15-membered-ring macrolide that presents a broad-spectrum antimicrobial activity against Gram-positive bacteria and atypical microorganisms but suffers from a poor diffusion across the outer-membrane of Gram-negative bacilli, including Pseudomonas aeruginosa (PA). However, AZM has demonstrated clinical benefits in patients suffering from chronic PA respiratory infections, especially cystic fibrosis patients. Since the rise of multidrug-resistant PA has led to a growing need for new therapeutic options, this macrolide has been proposed as an adjunctive therapy. Clinical trials assessing AZM in PA acute pneumonia are scarce. However, a careful examination of the available literature provides good rationales for its use in that context. In fact, 14- and 15-membered-ring macrolides have demonstrated immunomodulatory and immunosuppressive effects that could be of major interest in the management of acute illness. Furthermore, growing evidence supports a downregulation of PA virulence dependent on direct interaction with the ribosomes, and based on the modulation of several key regulators from the Quorum Sensing network. First highlighted in vitro, these interesting properties of AZM have subsequently been confirmed in the animal models. In this review, we systematically analyzed the literature regarding AZM immunomodulatory and anti-PA effects. In vitro and in vivo studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia.

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Section: Macrolides Influence On Cell Signalingmentioning

confidence: 99%

Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

et al. 2021

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“…By measuring the amount of chemical mediators, e.g. histamine or β-hexosaminidase, released from mast cells, previous studies have tried to determine the effects of macrolide antibiotics on the stabilization of mast cells [12,13,14,15]. However, due to the limitations of the methods used in molecular biology [16], the effects of these drugs on the exocytotic process could not directly been examined in mast cells.…”

Section: Introductionmentioning

confidence: 99%

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

Kazama¹,

Saito²,

Baba³

et al. 2016

Chemotherapy

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Background: Macrolides, such as clarithromycin, have antiallergic properties. Since exocytosis in mast cells is detected electrophysiologically via changes in membrane capacitance (Cm), the absence of such changes due to the drug indicates its mast cell-stabilizing effect. Methods: Employing the whole-cell patch clamp technique in rat peritoneal mast cells, we examined the effects of clarithromycin on Cm during exocytosis. Using a water-soluble fluorescent dye, we also examined its effect on deformation of the plasma membrane. Results: Clarithromycin (10 and 100 μM) significantly inhibited degranulation from mast cells and almost totally suppressed the GTP-γ-S-induced increase in Cm. It washed out the trapping of the dye on the surface of mast cells. Conclusions: This study provides for the first time electrophysiological evidence that clarithromycin dose-dependently inhibits the process of exocytosis. The mast cell-stabilizing action of clarithromycin may be attributable to its counteractive effect on plasma membrane deformation induced by exocytosis.

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β-Defensin Strengthens Antimicrobial Peritoneal Mast Cell Response

Agier

Brzezińska‐Błaszczyk

Różalska

et al. 2020

Journal of Immunology Research

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Mast cells (MCs) are engaged in the processes of host defense, primarily via the presence of receptors responsible for the detection of pathogen-associated molecular patterns (PAMPs). Since BDs are exclusively host defense molecules, and MCs can elicit the antimicrobial response, this study is aimed at determining whether BDs might be involved in MC pathogen defense. We found that defensin BD-2 significantly augments the mRNA and protein expression of Toll-like receptors (TLRs) and retinoic acid-inducible gene-I-like receptor (RLR) essential for the detection of viral molecules, i.e., TLR3, TLR7, TLR9, and RIG-I in mature tissue rat peritoneal MCs (PMCs). We established that BD-2 might stimulate PMCs to release proinflammatory and immunoregulatory mediators and to induce a migratory response. Presented data on IgE-coated PMC upon BD-2 treatment suggest that in the case of allergies, there is an enhanced MC immune response and cell influx to the site of the ongoing infection. In conclusion, our data highlight that BD-2 might strongly influence MC features and activity, mainly by strengthening their role in the inflammatory mechanisms and controlling the activity of cells participating in antimicrobial processes.

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Inhibitory action of roxithromycin on histamine release and prostaglandin D2 production from β-defensin 2-stimulated mast cells

Cited by 3 publications

References 24 publications

Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

β-Defensin Strengthens Antimicrobial Peritoneal Mast Cell Response

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