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Macrolide antibiotics like azithromycin increase lipopolysaccharide-induced IL-8 production by human gingival
1Department of Pharmacology, Matsumoto Dental University, 1780 Gobara, Hirooka, Shiojiri, Nagano 399-0781, Japan.
Objective:
Macrolide antibiotics are reported to modulate the production of cytokines in various type of cells. We examined the effect of macrolide antibiotics on inflammatory cytokines (IL-6 and IL-8) and chemical mediator (PGE(2)) and also matrix metalloproteinases (MMPs) productions by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS).
Methods:
The effect of macrolide antibiotics [erythromycin (EM), azithromycin (AZM) and josamycin (JOM)] on HGFs proliferation were examined by MTT assay. HGFs were treated with LPS from Porphyromonas gingivalis (PgLPS) and macrolide antibiotics, and IL-6, IL-8 and PGE(2) levels were evaluated by ELISA. MMPs were detected by gelatin zymography.
Results:
AZM slightly but significantly decreased HGFs proliferation, while EM and JOM did not affected. AZM increased PgLPS-induced IL-8 production dose-dependently, while AZM did not alter IL-6 and PGE2 productions. EM and JOM did not altered PgLPS-induced IL-6, IL-8 and PGE(2) productions. All macrolide antibiotics did not alter MMPs production. These results indicate that macrolide antibiotics have no direct anti-inflammatory effect. However, the use of the inhibitors of cell signaling pathway failed to reveal the mechanism that AZM enhanced PgLPS-induced IL-8 production.
Conclusion:
These results suggest macrolide antibiotics have an indirect anti-inflammatory effect as a result of their antimicrobial properties. Because AZM increased LPS-induced IL-8 production by HGFs, the possibility is considered that neutrophils may be migrated to periodontal tissue and phagocytize the periodontopathic bacteria more efficiently.
Insights
Macrolide antibiotics like azithromycin (AZM) did not show direct anti-inflammatory effects on human gingival fibroblasts. However, AZM increased IL-8 production, potentially enhancing neutrophil response to periodontal bacteria.
Area of Science:
- Periodontology
- Microbiology
- Immunology
Background:
- Macrolide antibiotics are known to modulate cytokine production.
- The effects of macrolides on inflammatory mediators in periodontal tissues require further investigation.
Purpose of the Study:
- To investigate the impact of macrolide antibiotics (erythromycin, azithromycin, josamycin) on inflammatory cytokine and mediator production by human gingival fibroblasts stimulated with lipopolysaccharide (LPS).
- To assess the effect of these macrolides on matrix metalloproteinases (MMPs) in the same cellular model.
Main Methods:
- Human gingival fibroblasts (HGFs) proliferation was assessed using MTT assay.
- Cytokine (IL-6, IL-8) and prostaglandin E2 (PGE2) levels were quantified via ELISA after LPS and macrolide treatment.
- MMP activity was detected using gelatin zymography.
Main Results:
- Azithromycin (AZM) slightly reduced HGF proliferation; erythromycin (EM) and josamycin (JOM) did not affect it.
- AZM dose-dependently increased LPS-induced IL-8 production but did not affect IL-6 or PGE2.
- EM and JOM did not alter LPS-induced IL-6, IL-8, or PGE2 production. MMP production remained unaffected by all macrolides.
- No direct anti-inflammatory effect was observed, and the mechanism for AZM's enhancement of IL-8 production was not elucidated.
Conclusions:
- Macrolide antibiotics may exert an indirect anti-inflammatory effect through their antimicrobial properties.
- AZM's enhancement of LPS-induced IL-8 production could promote neutrophil migration to periodontal tissues, aiding in the clearance of periodontopathic bacteria.
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