• 생명과학회지
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• 제30권1호
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• pp.106-112
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• 2020

아미노아실-트랜스퍼 리보핵산 합성효소-상호작용 다기능 단백질 2(AIMP2)는 여러 tRNA 합성효소들과의 결합체를 이루게 하는 기능을 하며, DNA 손상에 대한 반응으로 세포사멸 활성을 나타낼 수 있다. DNA에 손상이 발생하면 AIMP2는 MDM2 공격으로부터 p53을 보호하기 위해 MDM2에 결합한다. TGF-β 신호에서 AIMP2는 세포 핵으로 들어가 FUSE 결합 단백질(FBP)과 결합하여 c-myc을 억제한다. TNF 수용체 관련 인자 2(TRAF2)는 c-Jun N-말단 키나아제(JNK), NF-κB 및 p38 미토겐 활성화 단백질 키나아제(MAPKs)의 신호에서 실행되는 두 수용체, TNF 수용체 1과 2 사이의 중요한 중재자이다. TARF2는 TNF-α 신호에서 JNK와 NF-κB의 활성화에 필요하며, 세포사멸 신호를 막는 중재자 역할을 수행한다. 또한 TNF-α 신호에서 AIMP2는 세포사멸을 향상시킨다. 이 신호에서, AIMP2는 TRAF2를 분해하는 것으로 잘 알려진 E3 유비키틴 효소인 c-IAP1과의 결합을 향상시킨다. AIMP2, TRAF2 및 c-IAP1을 포함한 복합체의 형성은 proteasome을 매개로 하여 TRAF2의 분해를 초래한다. 이러한 연구 결과는 AIMP2가 TNF-α 신호에서 직접적인 상호작용을 통해 TRAF2를 하향 조절시켜 세포사멸을 유도할 수 있음을 시사한다.

• 한국컴퓨터정보학회논문지
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• 제25권6호
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• pp.165-170
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• 2020

본 논문에서는 스코폴레틴이 알츠하이머병 신경염증보호제로서의 가능성을 제안하기 위해 미세아교세포 BV-2에서 아밀로이드베타 올리고머(Aβ_1-42)로 유도된 염증을 억제하는지 확인하였다. 또한, 염증관련 사이토카인 및 염증매개인자가 어떠한 메커니즘으로 조절되는지 확인하였다. 알츠하이머병은 가장 흔한 신경 퇴행성 질환이지만, 특정 병인을 알 수 없는 질환이며, 이를 해결하기 위해 많은 연구에서 노력을 기울이고 있다. 우리는 먼저 스코폴레틴과 Aβ_1-42가 BV-2 세포에 독성을 보이는지 확인하기 위해 CCK-8 assay 방법으로 세포 생존율을 측정하였다. Western Blot을 통해 Aβ_1-42로 유도된 염증반응에서 interleukin 1 beta (IL-1β), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor-κB (NF-κB)의 발현정도를 분석하였다. ANOVA 분석법을 통해 Aβ_1-42를 단독 처리한 BV-2 세포와 스코폴레틴을 전 처리한 BV-2 세포에서 단백질 발현 차이를 비교하였다. 그 결과 스코폴레틴을 전 처리한 BV-2 세포에서 IL-1β, COX-2, iNOS, NF-κB 발현수준이 유의미하게 감소되었다 (p value < 0.05). 따라서 본 연구는 향후 스코폴레틴이 알츠하이머병의 신경염증보호제로서 개발 가치가 있음을 제시하였다.

• 생명과학회지
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• 제32권7호
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• pp.491-500
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• 2022

HK표고버섯균사체(HK shiitake mushroom mycelium, HKSMM)는 간 건강 개별 인정 건강기능식품이다. LPS로 활성화된 RAW 264.7 세포에서 HKSMM50 (HKSMM의 50% ethanol 수용액 추출물)의 항염증효과를 연구하였다. AHCC는 positive control로 사용하였다. LPS로 활성화된 RAW 264.7 세포에 HKSMM50 및 AHCC를 처리(0, 20, 100, 500 ㎍/ml)하고 24시간 배양하여 배양물의 염증 관련 인자는 ELISA kits로, 세포에 함유된 iNOS와 COX-2 protein 발현은 Western blotting으로 측정하였다. HKSMM50는 LPS 처리에 비해 농도 의존적으로 NF-κB 함량을 낮추었고, iNOS와 COX-2 protein 발현을 억제하여 NO와 PGE₂ 함량을 낮추었다. 더불어 HKSMM50는 LPS 처리에 비해 IL-1β, TNF-α, IL-4 및 IL-6의 함량을 낮추었으나 SOD와 CAT의 활성은 증가시켰다. AHCC도 HKSSM50 처리와 비슷한 효과를 나타내었다. 이 결과는 HKSMM50이 LPS로 활성화된 RAW 264.7 세포에서 NF-κB 신호전달을 억제하여 항염증효과를 나타내었으며, HKSMM은 면역기능증진에 도움을 줄 수 있는 건강기능식품원료로 사용할 수 있을 것이다.

• Journal of Periodontal and Implant Science
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• 제52권2호
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• pp.127-140
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• 2022

Purpose: In dental avulsion, delayed replantation usually has an uncertain prognosis. After tooth replantation, complex inflammatory responses promote a return to periodontal tissue homeostasis. Various types of cytokines are produced in the inflammatory microenvironment, and these cytokines determine the periodontal tissue response. This study aimed to identify the gene expression profiles of replanted teeth and evaluate the functional differences between immediate and delayed replantation. Methods: Maxillary molars from Sprague-Dawley rats were extracted, exposed to a dry environment, and then replanted. The animals were divided into 2 groups according to the extra-oral time: immediate replantation (dry for 5 minutes) and delayed replantation (dry for 60 minutes). Either 3 or 7 days after replantation, the animals were sacrificed. Periodontal soft tissues were harvested for mRNA sequencing. Hallmark gene set enrichment analysis was performed to predict the function of gene-gene interactions. The normalized enrichment score (NES) was calculated to determine functional differences. Results: The hallmark gene sets enriched in delayed replantation at 3 days were oxidative phosphorylation (NES=2.82, Q<0.001) and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway (NES=1.52, Q=0.034). At 7 days after delayed replantation, TNF-α signaling via the NF-κB pathway (NES=-1.82, Q=0.002), angiogenesis (NES=-1.66, Q=0.01), and the transforming growth factor-beta signaling pathway (NES=-1.46, Q=0.051) were negatively highlighted. Conclusions: Differentially expressed gene profiles were significantly different between immediate and delayed replantation. TNF-α signaling via the NF-κB pathway was marked during the healing process. However, the enrichment score of this pathway changed in a time-dependent manner between immediate and delayed replantation.

• Journal of Veterinary Science
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• 제24권3호
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• pp.23.1-23.16
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• 2023

Background: Irritable bowel syndrome (IBS) is a functional bowel disorder (FBD). Objectives: To assess the therapeutic effects of paeoniflorin (PF) on IBS in rats. Method: Sixty male Sprague-Dawley rats were randomly divided into normal, model, positive drug, low-dose PF, medium-dose PF and high-dose PF groups (n = 10). After gavage for 2 consecutive weeks, the effect of PF on abdominal pain symptoms was assessed based on the abdominal withdrawal reflex (AWR) score, fecal water content and pathological changes in colon tissues. D-lactate, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, and phosphorylated nuclear factor kappa B (p-NF-κB) p65 was detected by Western blotting. The abundance and diversity changes of intestinal flora were explored using 16S ribosomal RNA sequencing. Result: In PF groups, the mucosal morphology of colon tissues was intact, and the glands were arranged neatly and structured clearly, without obvious inflammatory cell infiltration. Compared with the model group, PF groups had significantly elevated pain threshold, and mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin, decreased AWR score at 20 mmHg pressure, fecal water content, mRNA levels of IL-1β, TGF-β, and TNF-α, protein level of p-NF-κB p65 and level of serum D-lactate, and reduced levels of serum IL-1β, TGF-β, and TNF-α (p < 0.05, p < 0.01). PF groups had higher abundance of Lactobacillus, Akkermansia, Alistipes, and Bacteroides, but lower abundance of Desulfovibrio, Parasutterella, and Enterococcus than those of the model group. Conclusions: PF exerts therapeutic effects on IBS in rats probably by regulating the intestinal flora, and then up-regulating the expressions of ZO-1 and occludin in colon tissue while down-regulating the levels of IL-1β, TGF-β, TNF-α, D-lactate and p-NF-κB p65.

• 한국식품과학회지
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• 제52권3호
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• pp.249-254
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• 2020

우리는 한국생명공학연구원에서 제공한 소재를 탐색 후 ACE를 선별하였고 이 소재의 항염증 효능을 평가하였다. ACE는 세포독성이 없는 농도에서 LPS에 의한 iNOS의 발현과 NO의 생성을 유의적으로 억제하였다. ACE는 LPS에 의해 증가한 IKK, IκB, p65의 인산화와 IL-1β의 생성을 유의적으로 억제하였다. 이 논문은 ACE가 NO/iNOS 발현 및 NF-κB 신호 전달 경로의 억제를 통해 항염증 효능을 나타냄을 밝힌 최초의 논문으로서 의의를 가진다. 또한 이 결과를 바탕으로 ACE는 항염증 기능성식품 또는 의약품소재로써 활용가치가 높을 것으로 기대된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9835-9839
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• 2014

Fisetin is an effective compound extracted from lacquer which has been used in the treatment of various diseases. Preliminary data indicate that it also exerts specific anti-cancer effects. However, the manner in which fisetin regulates cancer growth remains unknown. In this study, we elucidated interference of fisetin with targets of the nuclear factor ${\kappa}B$ signal transduction pathway activated by Epstein-Barr virus encoding latent membrane protein 1 (LMP1)in nasopharyngeal carcinoma (NPC) cells, Results showed that fisetin inhibited the survival rate of CNE-LMP1 cells and NF-${\kappa}B$ activation caused by LMP1. Fisetin also suppressed nuclear translocation of NF-${\kappa}B$ (p65) and $I{\kappa}B{\alpha}$ phosphorylation, while inhibiting CyclinD1, all key targets of the NF-${\kappa}B$ signal transduction pathway. It was suggested that interference effects of fisetin with signal transduction activated by LMP1 encoded by the Epstein-Barr virus may play an important role in its anticancer potential.

• 한국축산식품학회지
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• 제43권1호
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• pp.101-112
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• 2023

This study aimed to assess whether genomic DNA (gDNA) extracted from Pediococcus acidilactici inhibits Porphyromonas gingivalis lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 cells. Pretreatment with gDNA of P. acidilactici K10 or P. acidilactici HW01 for 15 h effectively inhibited P. gingivalis LPS-induced mRNA expression of interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1. Although both gDNAs did not dose-dependently inhibit P. gingivalis LPS-induced mRNA expression of IL-6 and MCP-1, they inhibited IL-1β mRNA expression in a dose-dependent manner. Moreover, pretreatment with both gDNAs inhibited the secretion of IL-1β, IL-6, and MCP-1. When RAW 264.7 cells were stimulated with P. gingivalis LPS alone, the phosphorylation of mitogen-activated protein kinases (MAPKs) was increased. However, the phosphorylation of MAPKs was reduced in the presence of gDNAs. Furthermore, both gDNAs restored IκBα degradation induced by P. gingivalis LPS, indicating that both gDNAs suppressed the activation of nuclear factor-κB (NF-κB). In summary, P. acidilactici gDNA could inhibit P. gingivalis LPS-induced inflammatory responses through the suppression of MAPKs and NF-κB, suggesting that P. acidilactici gDNA could be effective in preventing periodontitis.

• 한방재활의학과학회지
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• 제30권3호
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• pp.71-87
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• 2020

Objectives Even though the various alternative herbal medicine has applied for osteoarthritis (OA) treatment, its scientific proof remains uncertain. The aim of the present study evaluates the effects of Chulbu-tang on inflammatory responses in a monosodium iodoacetate (MIA)-induced osteoarthritis rat model. Methods OA rat model was established by MIA injection in intra-joint of rats. 7 days after, OA rats except OA control rats were administrated Chulbu-tang (100 or 200 mg/kg) or Indomathacin (5 mg/kg) once a day for 14 days. The weight-bearing ability of hind paws were measured when group isolation 0, 7, and 14 days. Western blotting was performed to examine the knockdown/overexpressing efficiency of Chulbu-tang. In addition, cartilage destruction was measured histologically. Results Chulbu-tang treatment significantly reduced the protein expressions of inflammatory mediators such as inducible nitric oxide synthase and cyclooxygenase 2, and inhibited inflammatory cytokines including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6 through nuclear factor-kappa B (NF-κB) inactivation. Moreover, anti-oxidant enzymes such as superoxide dismutase and glutathione peroxidase-1/2 through nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway significantly increased. Our findings indicate that Chulbu-tang has the potential therapeutic effect on OA through inhibiting the inflammatory responses via inactivating NF-κB signaling pathway. In addition, upregulation of Nrf2 led to anti-oxidant effects. Conclusions Taken together, Chulbu-tang is believed to have antioxidant, anti-inflammatory effects, and cartilage protection for arthritis-causing rats.

• Journal of Microbiology and Biotechnology
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• 제32권1호
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• pp.81-90
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• 2022

Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers, and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. The anti-inflammatory effects of IVSK were evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of the inflammatory mediators interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1), and the mRNA expression of IL-6, IL-8, MCP-1, and IL-1β. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα, and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, while nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.