Vargas Breno da Silva, Vargas Bruno Sérgio Ferreira, Clemente-Napimoga Juliana Trindade, Hammock Bruce D, Abdalla Henrique B, Van Dyke Thomas E, Napimoga Marcelo H
Laboratory of Neuroimmune Interface of Pain Research, Faculdade São Leopoldo Mandic, Instituto de Pesquisa São Leopoldo Mandic, Campinas, Brazil.
Department of Entomology and UCD Comprehensive Cancer Center, University of California, Davis, California, USA.
J Periodontal Res. 2025 Mar;60(3):278-286. doi: 10.1111/jre.13350. Epub 2024 Sep 29.
Periodontitis is a prevalent inflammatory disorder affecting the oral cavity, driven by dysbiotic oral biofilm and host immune response interactions. While the major clinical focus of periodontitis treatment is currently controlling oral biofilm, understanding the immune response is crucial to prevent disease progression. Soluble epoxide hydrolase (sEH) inhibition has shown promise in preventing alveolar bone resorption. Triggering receptors expressed on myeloid cells (TREMs) play pivotal roles in regulating inflammation and bone homeostasis, and dysregulation of TREM signaling is implicated in periodontitis. Here, we investigated the impact of sEH inhibition on TREM 1 and 2 expression, associated with inflammatory cytokines, and histologically assessed the inflammatory infiltrate in periodontal tissue.
The experimental periodontitis model was induced by placing a ligature around the upper second molar. For 14 days, animals were treated daily with a sEH inhibitor (TPPU) or vehicle. The alveolar bone loss was examined using a methylene blue stain. Gingival tissues were used to measure the mRNA expression of TREM-1, TREM-2, IKKβ, NF-κB, IL-1β, IL-6, IL-8, and TNF-α by RT-qPCR. Another set of experiments was performed to determine the histological inflammatory scores.
In a ligature-induced periodontitis model, sEH inhibition prevented alveolar bone loss and reduced TREM1 expression, albeit with a slight elevation compared to the disease-free group. In contrast, TREM2 expression remained elevated, suggesting sustained immunomodulation favoring resolution. The inhibition of sEH reduced the expression of NF-κB, IL-1β, and TNF-α, while no differences were found in the expression of IL-6, IL-8, and IKKβ. In histological analysis, sEH inhibition reduced the inflammatory leukocyte infiltrate in periodontal tissues close to the ligature.
These findings underscore the potential of sEH inhibition to modulate periodontal inflammation by regulating TREM-1 alongside decreased IL-1β and TNF-α expression, highlighting a promising therapeutic approach for periodontitis management.
牙周炎是一种影响口腔的常见炎症性疾病，由口腔生物膜生态失调与宿主免疫反应相互作用所驱动。虽然目前牙周炎治疗的主要临床重点是控制口腔生物膜，但了解免疫反应对于预防疾病进展至关重要。可溶性环氧化物水解酶（sEH）抑制在预防牙槽骨吸收方面已显示出前景。髓系细胞上表达的触发受体（TREMs）在调节炎症和骨稳态中起关键作用，TREM信号失调与牙周炎有关。在此，我们研究了sEH抑制对与炎症细胞因子相关的TREM 1和2表达的影响，并通过组织学评估了牙周组织中的炎症浸润情况。
通过在上颌第二磨牙周围放置结扎线诱导建立实验性牙周炎模型。连续14天，动物每天接受sEH抑制剂（TPPU）或赋形剂治疗。使用亚甲蓝染色检查牙槽骨丧失情况。用牙龈组织通过逆转录定量聚合酶链反应（RT-qPCR）测量TREM-1、TREM-2、IKKβ、NF-κB、IL-1β、IL-6、IL-8和TNF-α的mRNA表达。进行另一组实验以确定组织学炎症评分。
在结扎诱导的牙周炎模型中，sEH抑制可预防牙槽骨丧失并降低TREM1表达，尽管与无疾病组相比略有升高。相比之下，TREM2表达仍然升高，表明有利于炎症消退的持续免疫调节。sEH的抑制降低了NF-κB、IL-1β和TNF-α的表达，而IL-6, IL-8和IKKβ的表达未发现差异。在组织学分析中，sEH抑制减少了结扎线附近牙周组织中的炎症白细胞浸润。
这些发现强调了sEH抑制通过调节TREM-1以及降低IL-1β和TNF-α表达来调节牙周炎症的潜力，突出了一种有前景的牙周炎治疗方法。
