Roles of TLR2, TLR4, NOd2, and NOd1 in Pulp Fibroblasts
Roles of TLR2, TLR4, NOd2, and NOd1 in Pulp Fibroblasts
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DOI：
10.1177/0022034509341779
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发表时间：
2009-08-01
影响因子：
7.6
通讯作者：
Matsuo, T.
中科院分区：
文献类型：
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作者：
Hirao, K.;Yumoto, H.;Matsuo, T.
牙髓成纤维细胞表达多种促炎介质，导致牙髓炎进展过程中炎症细胞明显浸润。我们假设牙髓成纤维细胞在识别入侵的龋齿相关细菌和随后的先天免疫反应中发挥作用。我们通过RT-PCR和流式细胞术发现TLR2、NOD1和NOD2在人牙髓成纤维细胞（HDPF）中有明显表达，TLR4在HDPF中有微弱表达。我们还观察到各种促炎介质，包括细胞因子、趋化因子、粘附分子、前列腺素E-2及其关键酶COX-2，而不是iNOS或caspase-1，在这些TLR和NOD激动剂的刺激下显着上调。此外，NOD2激动剂与TLR2（而不是TLR4）激动剂协同作用，刺激HDPF中促炎介质的产生。这些发现提示HDPF中的TLR2、TLR4、NOD2和NOD1是功能性受体，而NOD2在牙髓免疫应答中是通过TLR2传递的信号调节剂，导致牙髓炎的进展。缩写：HDPF，人牙髓成纤维细胞；IL,白介素;MCP-1，单核细胞化学引诱蛋白1；干扰素- γ诱导蛋白-10；有限合伙人,脂多糖;细胞间粘附分子-1；PG,前列腺素;iNOS，诱导型一氧化氮合酶；模式识别受体；PAMP，模式相关分子模式；toll样受体；NOD，核苷酸结合寡聚化结构域；MDP muramyldipeptide;nf - κ B，核因子κ B；逆转录聚合酶链式反应；DMEM， Dulbecco改良的Eagle培养基；- -d -谷氨酰胺-中二氨基戊酸；iE-Lys gamma-D-glutamyl-lysine;MDP-LL N-acetylmuramyl-L-alanyl-L-isoglutamine;甘油醛-3-磷酸脱氢酶；ELISA，酶联免疫吸附试验；VCAM-1，血管细胞粘附分子-1；FITC，异硫氰酸荧光素；cox - 2, cyclooxygenase-2。
Pulp fibroblasts express various pro-inflammatory mediators leading to marked infiltration of inflammatory cells in the progression of pulpitis. We hypothesized that pulp fibroblasts play roles in the recognition of invaded caries-related bacteria and the subsequent innate immune responses. We found clear expressions of TLR2, NOD1, and NOD2 and a faint expression of TLR4 in human dental pulp fibroblasts (HDPF) by RT-PCR and flow cytometry. We also observed that various pro-inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostaglandin E-2 and its key enzyme COX-2, not iNOS or caspase-1, were markedly up-regulated by stimulation with these TLR and NOD agonists. More over, the NOD2 agonist acted synergistically with the TLR2, not the TLR4, agonist to stimulate the production of pro-inflammatory mediators in HDPF. These findings indicate that TLR2, TLR4, NOD2, and NOD1 in HDPF are functional receptors, and NOD2 is a modulator of signals transmitted through TLR2 in pulpal immune responses, leading to progressive pulpitis. Abbreviations: HDPF, human dental pulp fibroblasts; IL, interleukin; MCP-1, monocyte-chemoattractant protein-1; IP-10, interferon-gamma-inducible protein-10; LPS, lipopolysaccharide; ICAM-1, intercellular adhesion molecule-1; PG, prostaglandin; iNOS, inducible nitric oxide synthase; PRR, pattern recognition receptor; PAMP, pattern-associated molecular pattern; TLR, Toll-like receptor; NOD, nucleotide-binding oligomerization domain; MDP, muramyldipeptide; NF-kappa B, nuclear factor-kappa B; RT-PCR, reverse-transcription polymerase chain-reaction; DMEM, Dulbecco's modified Eagle's medium; iE-DAP, gamma-D-glutamyl-meso-diaminopimelic acid; iE-Lys, gamma-D-glutamyl-lysine; MDP-LL, N-acetylmuramyl-L-alanyl-L-isoglutamine; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ELISA, enzyme-linked immunosorbent assay; VCAM-1, vascular cell adhesion molecule-1; FITC, fluorescein isothiocyanate; COX-2, cyclooxygenase-2.