Effects of Indomethacin, Dexamethasone, and Erythromycin on Endotoxin-Induced Intraepithelial Mucus Production of Rat Nasal Epithelium

Takahashi, Yukimitsu; Shimizu, Takeshi; Sakakura, Yasuo

doi:10.1177/000348949710600813

Cited by 26 publications

(14 citation statements)

References 17 publications

(8 reference statements)

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“…These results indicate that neutrophil elastase is an important mediator of endotoxin-induced epithelial mucus production; however, other inflammatory mediators are also probably involved in this change. In a previous study, we showed that intraperitoneal injection of indomethacin (an inhibitor of the cyclooxygenase pathway) partially inhibits endotoxin-induced mucus production, 11 but that the cysteinyl LT (LTC4, LTD4, and LTE4) antagonist ONO-1078 did not effeet this change (data not shown). These findings suggest that prostaglandins, but not cysteinyl LTs, mediate endotoxin-induced mucus production.…”

Section: Discussionmentioning

confidence: 90%

Role of Neutrophil Elastase in Endotoxin-Induced Mucus Hypersecretion in Rat Nasal Epithelium

Shimizu¹,

Takahashi²,

Majima³

et al. 2000

Ann Otol Rhinol Laryngol

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In the present study, hypertrophic and metaplastic changes of goblet cells were induced in rat nasal epithelium by intranasal instillation of endotoxin or elastase. A significant increase in the amount of intraepithelial mucosubstance was observed after 24 hours during 3 days of instillation. The elastase-induced mucus production was not inhibited in neutrophil-depleted rats, but the endotoxin-induced change was significantly inhibited. Intranasal instillation of the neutrophil elastase inhibitor ONO-5046 partially inhibited the endotoxin-induced mucus production. Epithelial mucus secretion was evaluated by the temporary decrease in the amount of intraepithelial mucosubstance. The endotoxin-induced mucus secretion peaked 3 to 6 hours after intranasal instillation, coinciding with the peak of the intraepithelial neutrophil infiltration. The elastase-induced mucus secretion peaked 1 to 3 hours after intranasal instillation; intraepithelial neutrophil infiltration was not induced by elastase. These results indicate that neutrophil elastase is an important mediator of the intraepithelial mucus synthesis and secretion induced by endotoxin.

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Section: Discussionmentioning

confidence: 90%

Role of Neutrophil Elastase in Endotoxin-Induced Mucus Hypersecretion in Rat Nasal Epithelium

Shimizu¹,

Takahashi²,

Majima³

et al. 2000

Ann Otol Rhinol Laryngol

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“…20 Other macrolides such as erythromycin have been shown to inhibit hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium, as well as inhibit the proliferation of human mononuclear cells. 21,22 Azithromycin along with clarithromycin are reported to induce apoptosis of activated lymphocytes. 23 In previous studies in our laboratory, azithromycin was also observed to cause reversible autophagy in rabbit tracheal SMCs, but not apoptosis, as well as reversible inhibition of the proliferation.…”

Section: Discussionmentioning

confidence: 99%

Azithromycin reduces the viability of human bronchial smooth muscle cells

et al. 2010

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The macrolide antibiotic azithromycin has an antiproliferative and autophagic effect on rabbit tracheal smooth muscle cells (SMCs). The purpose of this study is to investigate the effect of azithromycin on human bronchial SMCs. Human bronchial SMCs were treated with azithromycin (10 À5 M) in the presence or absence of 10% fetal bovine serum (FBS). Cell number was estimated using the Cell Titer 96 AQ ueous One Solution Assay. Induction of autophagy was studied by observation of cell morphology in cells treated or not with the autophagy inhibitor, 3-methyladenine (3-MA), as well as by Lysotracker Red staining of lysosomes. Activation of apoptosis was assessed with flow cytometry after annexin staining. Incubation with azithromycin for 24, 48 or 72 h reduced viability in FBS-deprived cells, as well as cells cultured in FBS-containing medium. Azithromycin treatment resulted in the formation of cytoplasmic vacuoles that could not be prevented by 3-MA. Furthermore, 3-MA did not reverse the effect of azithromycin on the viability of SMCs. There was an increase in the number of lysosomes in cells treated with azithromycin. Finally, azithromycin increased the percentage of early apoptotic cells. In conclusion, azithromycin reduces the viability of human bronchial SMCs possibly by leading to apoptotic cell death.

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“…Berger et al [9••] suggest that for glandular subtypes of disease, the use of macrolide antibiotics might represent a reasonable option for targeted therapy. Macrolide antibiotics have been shown to cause marked reduction in mucus hypersecretion in addition to their antibiotic actions [47].…”

Section: Discussionmentioning

confidence: 99%

The new histologic classification of chronic rhinosinusitis

Malekzadeh

McGuire

2003

Curr Allergy Asthma Rep

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Two histologic patterns of disease are found in chronic rhinosinusitis. The first is dominated by eosinophilia and polypoid changes. Glandular hyperplasia and hypertrophy characterize the second. We present the evidence supporting the existence of these two patterns of disease and link these histologic patterns to the larger pathophysiologic processes that drive them. This histologic classification should be acknowledged both in the clinical setting and in laboratory research of chronic rhinosinusitis.

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Effects of Indomethacin, Dexamethasone, and Erythromycin on Endotoxin-Induced Intraepithelial Mucus Production of Rat Nasal Epithelium

Cited by 26 publications

References 17 publications

Role of Neutrophil Elastase in Endotoxin-Induced Mucus Hypersecretion in Rat Nasal Epithelium

Role of Neutrophil Elastase in Endotoxin-Induced Mucus Hypersecretion in Rat Nasal Epithelium

Azithromycin reduces the viability of human bronchial smooth muscle cells

The new histologic classification of chronic rhinosinusitis

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