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环二核苷酸和脂多糖对细胞反应的激活作用：牙龈成纤维细胞的蛋白质组学研究

Activation of cellular responses by cyclic dinucleotides and lipopolysaccharide: a proteomic study on gingival fibroblasts.

作者信息

Elmanfi Samira, Onyedibe Kenneth I, Aryal Uma K, Könönen Eija, Sintim Herman O, Gürsoy Ulvi Kahraman

机构信息

Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland.

Department of Chemistry, Purdue University, West Lafayette, USA.

出版信息

J Oral Microbiol. 2024 Dec 9;17(1):2431453. doi: 10.1080/20002297.2024.2431453. eCollection 2025.

DOI:10.1080/20002297.2024.2431453
PMID:39669221
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11632945/
Abstract

BACKGROUND

Bacterial cyclic dinucleotides (CDNs), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) upregulate interferon signaling proteins of human gingival fibroblasts (HGFs). However, the simultaneous effect of bacterial CDNs and lipopolysaccharides (LPS) on the HGF proteome is unknown.

AIM

The aim was to apply an unbiased proteomics approach to evaluate how simultaneous exposure to CDNs and (Pg) LPS affect the global proteome of HGFs.

METHODS

The proteomic responses of HGFs were examined under three different treatment conditions (c-di-AMP+Pg LPS, c-di-GMP+Pg LPS, and Pg LPS alone) by label-free quantitative mass spectrometry analysis.

RESULTS

Simultaneous exposure to CDNs and Pg LPS significantly upregulated innate immunity-related and interferon signaling-related proteins, such as ubiquitin-like protein ISG15 (ISG15), deoxynucleoside triphosphate triphosphohydrolase (SAMHD1), interferon regulatory factor 9 (IRF-9), interferon-induced GTP-binding protein Mx (MX)1, and MX2. Interferon signaling pathway was the most significantly regulated canonical pathway in both CDN treatment groups.

CONCLUSION

Simultaneous exposure to CDNs and Pg LPS stimulates the periodontal immune response by activating the anti-microbial cellular responses of HGFs with some notable differences from individual exposures.

摘要

背景

细菌环二核苷酸（CDNs）、环二鸟苷单磷酸（c-di-GMP）和环二腺苷单磷酸（c-di-AMP）可上调人牙龈成纤维细胞（HGFs）的干扰素信号蛋白。然而，细菌CDNs与脂多糖（LPS）对HGF蛋白质组的联合作用尚不清楚。

目的

应用非靶向蛋白质组学方法评估同时暴露于CDNs和牙龈卟啉单胞菌（Pg）LPS如何影响HGF的整体蛋白质组。

方法

通过无标记定量质谱分析，在三种不同处理条件下（c-di-AMP+Pg LPS、c-di-GMP+Pg LPS和单独的Pg LPS）检测HGF的蛋白质组反应。

结果

同时暴露于CDNs和Pg LPS显著上调了先天免疫相关和干扰素信号相关蛋白，如泛素样蛋白ISG15、脱氧核苷三磷酸三磷酸水解酶（SAMHD1）、干扰素调节因子9（IRF-9）、干扰素诱导的GTP结合蛋白Mx1和Mx2。在两个CDN处理组中，干扰素信号通路是调节最显著的经典通路。

结论

同时暴露于CDNs和Pg LPS通过激活HGF的抗菌细胞反应刺激牙周免疫反应，与单独暴露有一些显著差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/f17a3c4b9af0/ZJOM_A_2431453_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/e32aa99bf370/ZJOM_A_2431453_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/11d2208596cc/ZJOM_A_2431453_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/30e4917ba68f/ZJOM_A_2431453_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/8071d93990d2/ZJOM_A_2431453_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/b27e4d3e5174/ZJOM_A_2431453_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/98c51708a73c/ZJOM_A_2431453_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/f17a3c4b9af0/ZJOM_A_2431453_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/e32aa99bf370/ZJOM_A_2431453_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/11d2208596cc/ZJOM_A_2431453_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/30e4917ba68f/ZJOM_A_2431453_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/8071d93990d2/ZJOM_A_2431453_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/b27e4d3e5174/ZJOM_A_2431453_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/98c51708a73c/ZJOM_A_2431453_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ad2/11632945/f17a3c4b9af0/ZJOM_A_2431453_F0007_OC.jpg

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