Effect of Azithromycin on Proinflammatory Cytokine Production in Gingival Fibroblasts and the Remodeling of Periodontal Tissue.

Takatoshi Nagano,Yuji Matsushima,Takao Yamaguchi,Sohtaro Kajiyama,Satoshi Shirakawa,Akihiro Yashima,Kazuhiro Gomi,Takuma Suzuki

doi:10.3390/jcm10010099

Takatoshi Nagano, Yuji Matsushima + Show 6 more

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https://doi.org/10.3390/jcm10010099

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Abstract

Previous reports have shown that azithromycin (AZM), a macrolide antibiotic, affects collagen synthesis and cytokine production in human gingival fibroblasts (hGFs). However, there are few reports on the effect of AZM on human periodontal ligament fibroblasts (hPLFs). In the present study, we comparatively examined the effects of AZM on hGFs and hPLFs. We monitored the reaction of AZM under lipopolysaccharide (LPS) stimulation or no stimulation in hGFs and hPLFs. Gene expression analyses of interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), and Type 1 collagen were performed using reverse transcription-polymerase chain reaction (RT-PCR). Subsequently, we performed Western blotting for the analysis of the intracellular signal transduction pathway. In response to LPS stimulation, the gene expression levels of IL-6 and IL-8 in hGFs increased due to AZM in a concentration-dependent manner, and phosphorylation of nuclear factor kappa B (NF-κB) was also promoted. Additionally, AZM caused an increase in MMP-1 expression in hGFs, whereas it did not affect the expression of any of the analyzed genes in hPLFs. Our findings indicate that AZM does not affect hPLFs and acts specifically on hGFs. Thus, AZM may increase the expression of IL-6 and IL-8 under LPS stimulation to modify the inflammatory response and increase the expression of MMP-1 to promote connective tissue remodeling.

Highlights

We previously demonstrated the clinical utility of full-mouth as well as partialmouth scaling and root planing (SRP) with the administration of the macrolide antibiotic azithromycin (AZM) [1,2,3,4]
These findings indicate that an increased production of inflammatory cytokines in human gingival fibroblasts (hGFs) may be caused by the effects of AZM due to LPS stimulation
Applying AZM to periodontal treatment may produce various secondary benefits and demonstrate efficacy in the clinical setting. These findings suggest that when full-mouth SRP (FM-SRP) is performed with AZM administration, AZM amplifies the gene expression of IL-6 and IL-8, which are involved in neutrophil migration in the inflamed gingival region

Summary

Introduction

We previously demonstrated the clinical utility of full-mouth as well as partialmouth scaling and root planing (SRP) with the administration of the macrolide antibiotic azithromycin (AZM) [1,2,3,4]. Studies have indicated that while performing full-mouth SRP (FM-SRP) with AZM administration, inflammation was reduced and periodontal pockets improved rapidly within an extremely short period of time This appears to be the result of the synergistic effect of the control of periodontopathic bacteria due to the antibacterial action of AZM and mechanical plaque control by SRP. When other antibiotics were used in the same manner, results equivalent to or better than those of AZM could not be obtained [5], especially with regard to the reduction in inflammation of periodontal pockets during the early stage after treatment [6] It appears that the effect of AZM is not limited to its antibacterial action, suggesting the possible involvement of another mechanism. In 2008, Kim et al reported that AZM inhibits the proliferation

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