Oral bacterial infections substantially affect the development of various periodontal diseases and oral cancers. However, the molecular mechanisms underlying the association between Fusobacterium nucleatum (F. nucleatum ), a major periodontitis (PT)-associated pathogen, and these diseases require extensive research. Previously, our RNAsequencing analysis identified a few hundred differentially expressed genes in patients with PT and peri-implantitis (PI) than in healthy controls. Thus, in the present study using oral squamous cell carcinoma (OSCC) cells, we aimed to evaluate the effect of F. nucleatum infection on genes that are differentially regulated in patients with PT and PI. Human oral squamous cell carcinoma cell lines OSC-2O, HSC-4, and HN22 were used. These cells were infected with F. nucleatum at a multiplicity of infection of 100 for 3 hours at 37℃ in 5% CO2. Gene expression was then measured using reverse-transcription polymerase chain reaction. Among 18 genes tested, the expression of CSF3, an inflammation-related cytokine, was increased by F. nucleatum infection. Additionally, F. nucleatum infection increased the phosphorylation of AKT, p38 MAPK, and JNK in OSC-20 cells. Treatment with p38 MAPK (SB202190) and JNK (SP600125) inhibitors reduced the enhanced CSF3 expression induced by F. nucleatum infection. Overall, this study demonstrated that F. nucleatum promotes CSF3 expression in OSCC cells through p38 MAPK and JNK signaling pathways, suggesting that p38 MAPK and JNK inhibitors may help treat F. nucleatum-related periodontal diseases by suppressing CSF3 expression.

Agarum clathratum (A. clathratum) is a marine brown algal species that belongs to the Costariaceae family and has antioxidant and anti-microbial properties. However, the anti-inflammatory effects of A. clathratum and the molecular mechanisms involved have not been determined so far. This study aimed to investigate the anti-inflammatory effects of A. clathratum extracts in THP-1 macrophages stimulated by lipopolysaccharide (LPS) derived from Porphyromonas gingivalis. The THP-1 cells were differentiated with 12-O-tetradecanoylphorbol-13-acetate and treated with A. clathratum before LPS stimulation. Cell viability was assessed using the trypan blue exclusion assay. The expression of pro-inflammatory response-associated molecules was evaluated by quantitative real-time polymerase chain reaction and Western blot analysis. A. clathratum treatment inhibited the expression of interleukin-1β in LPS-stimulated THP-1 macrophages without causing any cytotoxicity. The anti-inflammatory effect of A. clathratum resulted in a significant repression of the JNK/c-Jun signaling axis, a key regulator in inflammation responses. This study highlights the possible role of A. clathratum in the inhibition of pro-inflammatory cytokines via suppression of the JNK/c-Jun signaling axis and suggests that A. clathratum could serve as a marine-derived anti-inflammatory agent in periodontitis.

Rutin은 메밀에 함유되어 있는 것으로 잘 알려져 있는 flavonoid 물질로서, 최근 연구들에서 rutin의 항염증 및 암예 방 활성이 보고되어져 왔다. 그러나, rutin의 암예방 활성과 관련된 분자생물학적 기전에 대한 연구는 아직까지 미비 한 실정이다. 따라서, 본 연구에서는 발암 과정 중 하나인 세포의 악성 변형을 EGF로 유도하여 rutin이 이를 억제하는 지 여부를 확인하는 실험을 진행하였으며, 그 분자생물학적 기전을 규명하고자 하였다. Soft agar assay 실험 결과, rutin은 EGF로 유도된 세포의 악성 변형을 25 μM, 50 μM 100 μM에서 농도별로 감소시켰다. 또한 EGF로 유도된 MEK/ERK 및 MKK4/JNK 신호전달체계의 인산화를 저해하였다. 그러나 이와는 대조적으로 rutin은 EGF로 유도된 MKK3/6/p38 신호전달체계 인산화는 감소시키지 못하는 것으로 확인되었다. 이상의 연구결과들은 rutin이 암화 과정 중 발생되는 세포의 악성변형 과정을 촉진시킨다고 잘 알려져 있는 MEK/ERK 및 MKK4/JNK 신호전달체계의 활성화 를 억제함으로써 암예방 활성을 나타낸다는 것을 제시하고 있으며, 이는 메밀의 생리활성 성분인 rutin의 암예방 생리 활성 소재로서의 이용 가능성을 보여주는 중요한 연구 결과라 할 수 있겠다. 또한 위 연구결과는 MEK/ERK 및 MKK4/JNK 신호전달 체계를 표적으로 하는 생리활성 소재 탐색에도 활용 가능할 것으로 생각되어진다.