Department of Periodontology, Institute of Oral Health Science, Ajou University School of Medicine, Suwon, Korea.
J Periodontal Res. 2021 Jun;56(3):462-470. doi: 10.1111/jre.12837. Epub 2021 Jan 5.
We previously reported that gingival fibroblasts (GFs) can be polarized into functionally distinct subtypes, immune-activating but tissue-destructive or tissue-reparative, in response to T helper (Th1) and Th2 stimuli, respectively. The purpose of this study was to evaluate the effect of polarization on GFs responses to oral bacteria.
Unprimed (GF(-)) and IFN-γ (GF(IFN-γ)) or IL-4 primed (GF(IL-4)) GFs were stimulated with live Fusobacterium nucleatum or Porphyromonas gingivalis. The mRNA expression of IL-1β, IL-4, LPS-recognizing components (Toll-like receptor (TLR) 4, CD14), molecules involved in antigen presentation (human leukocyte antigen (HLA)-ABC, HLA-DP, CD74, CD40), chemokines (C-X-C motif chemokine (CXCL)10, CXCL11, chemokine (C-C motif) ligand 20 (CCL20)), collagen type 1 alpha 1 (COL1A1), and matrix metalloproteinase (MMP)-1, and the protein levels of IL-1β, CD14, CXCL11, CCL20, and COL1A1 accumulated in supernatants were analyzed using real-time PCR and ELISA.
In response to oral bacteria, the GF(IFN-γ) significantly upregulated the expression of LPS-recognizing components, molecules involved in antigen presentation, CXCL10, and CXCL11, whereas the levels of IL-4 and COL1A1 were downregulated, compared with GF(-). The levels of IL-1β, CCL20, and MMP-1 from GF(IFN-γ) were differently regulated between both bacteria; F. nucleatum was synergistically upregulated, but P. gingivalis was downregulated. The GF(IL-4) stimulated with both bacteria upregulated the levels of IL-4, whereas the levels of TLR4 and chemokines were downregulated, compared with GF(-). The regulation of IL-1β, CD14, CXCL11, CCL20, and COL1A1 proteins showed a similar tendency with mRNA regulation.
Polarization of GFs with IFN-γ or IL-4 affected the way that GFs responded to oral bacteria through up or downregulation of inflammatory responses and extracellular matrix control.
我们曾报道过，牙龈成纤维细胞（GFs）在分别受到辅助性 T 细胞（Th1）和 Th2 刺激时，可以极化成为具有不同功能的亚型，分别表现为免疫激活和组织破坏性或组织修复性。本研究旨在评估极化对 GFs 对口腔细菌反应的影响。
未极化（GF(-)）和 IFN-γ（GF(IFN-γ)）或 IL-4 极化（GF(IL-4)）的 GFs 用活的核梭杆菌或牙龈卟啉单胞菌刺激。通过实时 PCR 和 ELISA 分析上清液中 IL-1β、IL-4、LPS 识别成分（Toll 样受体（TLR）4、CD14）、抗原呈递相关分子（人类白细胞抗原（HLA）-ABC、HLA-DP、CD74、CD40）、趋化因子（C-X-C 基序趋化因子（CXCL）10、CXCL11、趋化因子（C-C 基序）配体 20（CCL20））、胶原蛋白 1 型 alpha 1（COL1A1）和基质金属蛋白酶（MMP）-1 的 mRNA 表达，以及上清液中 IL-1β、CD14、CXCL11、CCL20 和 COL1A1 的蛋白水平。
在口腔细菌的刺激下，GF(IFN-γ) 显著上调 LPS 识别成分、抗原呈递相关分子、CXCL10 和 CXCL11 的表达，而 IL-4 和 COL1A1 的水平下调，与 GF(-)相比。GF(IFN-γ) 对两种细菌的 IL-1β、CCL20 和 MMP-1 水平的调节不同；F. nucleatum 被协同上调，而 P. gingivalis 被下调。两种细菌刺激的 GF(IL-4) 均上调了 IL-4 水平，而 TLR4 和趋化因子水平下调，与 GF(-)相比。IL-1β、CD14、CXCL11、CCL20 和 COL1A1 蛋白的调节与 mRNA 调节具有相似的趋势。
IFN-γ 或 IL-4 极化的 GFs 通过上调或下调炎症反应和细胞外基质控制来影响 GFs 对口腔细菌的反应方式。
