Suppressive Activity of Macrolide Antibiotics on Nitric Oxide Production from Nasal Polyp Fibroblasts In Vitro

Asano, Koichiro; Kamakazu, Kiyoaki; Hisamitsu, Tadashi; Suzaki, Harumi

doi:10.1080/00016480310002519

Cited by 12 publications

(14 citation statements)

References 20 publications

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“…Macrolides have also been reported to induce phospholipidosis in eukaryotic cells, the magnitude of which appears to correlate with anti-inflammatory activity [78, 79]. Macrolides have also been reported to suppress the production of another type of ROS, nitric oxide, by activated macrophages, presumably by interfering with the induction of inducible nitric oxide synthase via antagonism of NF- κ B [80, 81]. The anti-inflammatory interactions of macrolides with the cells of the innate immune system are summarised in Table 2.…”

Section: Effects Of Macrolides On Innate and Adaptive Immune Mechamentioning

confidence: 99%

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Steel

Theron

Cockeran

et al. 2012

Mediators of Inflammation

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Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

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Section: Effects Of Macrolides On Innate and Adaptive Immune Mechamentioning

confidence: 99%

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Steel

Theron

Cockeran

et al. 2012

Mediators of Inflammation

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“…In contrast, glandular and epithelial expressions of NOS-2 turned out to be significantly stronger in neutrophilic polyps. This suggests that macrolide antibiotics and fexofenadine hydrochloride, both significantly reducing the airway synthesis of nitric oxide, could be used as an adjuvant to glucocorticoids in the pharmacotherapy of nasal polyps, especially of their non-eosinophilic phenotype [34–36]. Our results contribute to a growing body of literature showing a locally elevated expression of inflammatory mediators in patients with chronic rhinosinusitis and polyps.…”

Section: Discussionmentioning

confidence: 58%

Differential expression of tumor necrosis factor α, interleukin 1β, nuclear factor κB in nasal mucosa among chronic rhinosinusitis patients with and without polyps

Plewka¹,

Grzanka²,

Drzewiecka³

et al. 2017

pdia

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Differential expression of tumor necrosis factor α, interleukin 1β, nuclear factor κB in nasal mucosa among chronic rhinosinusitis patients with and without polyps A b s t r a c t Introduction: The pathogenesis of nasal polyps is still not fully understood. Aim: To analyze the topography and intensity of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2), nitric oxide synthase 2 (NOS-2), and nuclear factor-κB (NF-κB) expressions in eosinophilic and neutrophilic polyps and in normal nasal mucosa. Material and methods: The study included specimens from 20 patients with eosinophilic polyps (more than 10% of eosinophils in inflammatory infiltrate), 20 individuals with neutrophilic polyps (predominance of neutrophils and less than 10% of eosinophils), and samples of normal nasal mucosa from 10 controls. The expressions of studied proteins in vascular endothelial cells, epithelial, stromal and glandular cells were determined immunohistochemically with specific monoclonal antibodies. Results: Irrespective of the cellular type, the intensity of expressions in eosinophilic and neutrophilic polyps was significantly higher than in the normal mucosa. Eosinophilic polyps were characterized by stronger expressions of TNF-α (in all cellular types), IL-1β (in endothelial, glandular and epithelial cells), NF-κB (in stromal and epithelial cells), COX-2 (in glandular and stromal cells), and NOS-2 (in endothelial and stromal cells). In contrast, neutrophilic polyps showed significantly stronger expressions of COX-2 (in epithelial and endothelial cells) and NOS-2 (in glandular and epithelial cells). In both phenotypes, the strongest expressions of all studied markers were documented in vascular endothelial cells. Conclusions: Inflammatory markers are involved in pathogenesis of both eosinophilic and neutrophilic polyps. Endothelial defects can play an important role in the development of nasal polyps.

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“…Among these NOS, iNOS that is generally not present in quiescent cells is often induced by inflammatory stimuli and mediates high levels of NO generation for long periods, resulting in tissue injury and mutations in cells [13,23,24]. Recent reports have clearly showed that macrolide antibiotics such as telithromycin and roxithromycin inhibit NO generation through the suppression of iNOS mRNA expression in vitro and in vivo [28-30]. These reports open the questions of whether CAM and M-4 on NO production is due to their inhibitory action of iNOS generation by iNOS mRNA expression or their suppression of iNOS activity to produce NO.…”

Section: Discussionmentioning

confidence: 99%

Suppression of nitric oxide production from nasal fibroblasts by metabolized clarithromycin in vitro

et al. 2010

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Background: Low-dose and long-term administration of 14-membered macrolide antibiotics, so called macrolide therapy, has been reported to favorably modify the clinical conditions of chronic airway diseases. Since there is growing evidence that macrolide antibiotic-resistant bacteria's spreaders in the populations received macrolide therapy, it is strongly desired to develop macrolide antibiotics, which showed only anti-inflammatory action. The present study was designed to examine the influence of clarithromycin (CAM) and its metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal polyp fibroblasts (NPFs) through the choice of nitric oxide (NO), which is one of important effector molecule in the development of airway inflammatory disease in vitro. Methods: NPFs (5 × 10 5 cells/ml) were stimulated with 1.0 μg/ml lipopolysaccharide (LPS) in the presence of agents for 24 hours. NO levels in culture supernatants were examined by the Griess method. We also examined the influence of agents on the phosphorylation of MAPKs, NF-B activation, iNOS mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours, respectively. Results: The addition of CAM (> 0.4 μg/ml) and M-4 (> 0.04 μg/ml) could suppress NO production from NPFs after LPS stimulation through the suppression of iNOS mRNA expression and NF-B activation. CAM and M-4 also suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the NO generation, even when 0.1 μg/ml of the agent was added to cell cultures. Conclusion:The present results may suggest that M-4 will be a good candidate for the agent in the treatment of chronic airway inflammatory diseases, since M-4 did not have antimicribiological effects on gram positive and negative bacteria.

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Suppressive Activity of Macrolide Antibiotics on Nitric Oxide Production from Nasal Polyp Fibroblasts In Vitro

Cited by 12 publications

References 20 publications

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Differential expression of tumor necrosis factor α, interleukin 1β, nuclear factor κB in nasal mucosa among chronic rhinosinusitis patients with and without polyps

Suppression of nitric oxide production from nasal fibroblasts by metabolized clarithromycin in vitro

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