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口腔角质形成细胞中CXCL9和CXCL10的抗菌活性及调控

Antimicrobial activity and regulation of CXCL9 and CXCL10 in oral keratinocytes.

作者信息

Marshall Alison, Celentano Antonio, Cirillo Nicola, Mignogna Michele D, McCullough Michael, Porter Stephen

机构信息

University College London, UCL Eastman Dental Institute, London, UK.

University Federico II of Naples, Department of Neuroscience, Reproductive and Odontostomatological Sciences, Naples, Italy.

出版信息

Eur J Oral Sci. 2016 Oct;124(5):433-439. doi: 10.1111/eos.12293. Epub 2016 Sep 27.

DOI:10.1111/eos.12293
PMID:27671889
Abstract

Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10 are dysregulated in oral inflammatory conditions, and it is not known if these chemokines target microorganisms that form oral biofilm. The aim of this study was to investigate the antimicrobial activity of CXCL9 and CXCL10 on oral microflora and their expression profiles in oral keratinocytes following exposure to inflammatory and infectious stimuli. Streptococcus sanguinis was used as a model and Escherichia coli as a positive control. The antimicrobial effect of CXCL9/CXCL10 was tested using a radial diffusion assay. mRNA transcripts were isolated from lipopolysaccharide (LPS)-treated and untreated (control) oral keratinocyte cell lines at 2-, 4-, 6-, and 8-h time-points of culture. The CXCL9/10 expression profile in the presence or absence of interferon-γ (IFN-γ) was assessed using semiquantitative PCR. Although both chemokines demonstrated antimicrobial activity, CXCL9 was the most effective chemokine against both S. sanguinis and E coli. mRNA for CXCL10 was expressed in control cells and its production was enhanced at all time-points following stimulation with LPS. Conversely, CXCL9 mRNA was not expressed in control or LPS-stimulated cells. Finally, stimulation with IFN-γ enhanced basal expression of both CXCL9 and CXCL10 in oral keratinocytes. Chemokines derived from oral epithelium, particularly CXCL9, demonstrate antimicrobial properties. Bacterial and inflammatory-stimulated up-regulation of CXCL9/10 could represent a key element in oral bacterial colonization homeostasis and host-defense mechanisms.

摘要

趋化因子(C-X-C基序)配体(CXCL)9和CXCL10在口腔炎症性疾病中表达失调,目前尚不清楚这些趋化因子是否靶向形成口腔生物膜的微生物。本研究旨在探讨CXCL9和CXCL10对口腔微生物群的抗菌活性及其在暴露于炎症和感染刺激后口腔角质形成细胞中的表达谱。以血链球菌为模型,大肠杆菌作为阳性对照。采用径向扩散试验检测CXCL9/CXCL10的抗菌效果。在培养的2、4、6和8小时时间点,从脂多糖(LPS)处理和未处理(对照)的口腔角质形成细胞系中分离mRNA转录本。使用半定量PCR评估在存在或不存在干扰素-γ(IFN-γ)的情况下CXCL9/10的表达谱。虽然两种趋化因子均表现出抗菌活性,但CXCL9是针对血链球菌和大肠杆菌最有效的趋化因子。CXCL10的mRNA在对照细胞中表达,并且在用LPS刺激后的所有时间点其产量均增加。相反,CXCL9的mRNA在对照或LPS刺激的细胞中未表达。最后,用IFN-γ刺激可增强口腔角质形成细胞中CXCL9和CXCL10的基础表达。源自口腔上皮的趋化因子,特别是CXCL9,具有抗菌特性。细菌和炎症刺激引起的CXCL9/10上调可能是口腔细菌定植稳态和宿主防御机制的关键因素。

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