• Journal of Animal Science and Technology
• /
• 제53권6호
• /
• pp.511-516
• /
• 2011

Fas gene known to associate with intramuscular fat content in Korean cattle was selected for DNA marker development. Fas (APO-1, CD95), a member of the tumor necrosis factor (TNF) receptor superfamily, is a cell membrane protein that mediates apoptosis (programmed cell death). We discovered single nucleotide polymorphisms (SNPs) within Fas gene in order to develop novel DNA markers at genomic level. Of this gene to search for SNP, sequences of whole exon and 1kb range of both front and back of the gene using 24 cattle were determined by direct-sequencing methods. As a result, 16 SNPs in exon, 37 SNPs in intron and 2 SNPs in promoter region, a total of 55 SNPs were discovered. In these SNPs, thirty-one common polymorphic sites were selected considering their allele frequencies, haplotype-tagging status and Linkage Disequilibrium (LD) for genotyping in larger-scale subjects. Selected SNPs were confirmed genotype through SNaPshot method (n=274) and were examined for possible genetic association of Fas polymorphisms with carcass weight (CWT), eye muscle area (EMA), and backfat thickness (BF). So, the SNP have been identified significant g.-12T>G, g.1112T>G and g.32548T>C. These results suggest that polymorphism of Fas gene was associated with meat quality traits in Hanwoo.

• Biomolecules & Therapeutics
• /
• 제29권2호
• /
• pp.220-226
• /
• 2021

The role of particulate matter (PM) in health problems including cardiovascular diseases (CVD) and pneumonia is becoming increasingly clear. Polycyclic aromatic hydrocarbons, major components of PM, bind to aryl hydrocarbon receptor (AhRs) and promote the expression of CYP1A1 through the AhR pathway in keratinocytes. Activation of AhRs in skin cells is associated with cell differentiation in keratinocytes and inflammation, resulting in dermatological lesions. Oleanolic acid, a natural component of L. lucidum, also has anti-inflammation, anticancer, and antioxidant characteristics. Previously, we found that PM10 induced the AhR signaling pathway and autophagy process in keratinocytes. Here, we investigated the effects of oleanolic acid on PM10-induced skin aging. We observed that oleanolic acid inhibits PM10-induced CYP1A1 and decreases the increase of tumor necrosis factor-alpha and interleukin 6 induced by PM10. A supernatant derived from keratinocytes cotreated with oleanolic acid and PM10 inhibited the release of matrix metalloproteinase 1 in dermal fibroblasts. Also, the AhR-mediated autophagy disruption was recovered by oleanolic acid. Thus, oleanolic acid may be a potential treatment for addressing PM10-induced skin aging.

• Molecules and Cells
• /
• 제44권12호
• /
• pp.893-899
• /
• 2021

BLT2 is a low-affinity receptor for leukotriene B₄, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB₄ [leukotriene B₄] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-lipoxygenase (5-LO) and 12-LO, which are synthesizing enzymes for LTB₄ and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1β [interleukin-β] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.

• IMMUNE NETWORK
• /
• 제21권5호
• /
• pp.37.1-37.17
• /
• 2021

Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial. Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.

• 한국자원식물학회지
• /
• 제36권1호
• /
• pp.15-25
• /
• 2023

이삭물수세미는 민간에서는 전초를 고름, 염증 등에 약용으로 사용하였으나, 염증에 대한 연구가 미비한 상황이다. 이에 본 연구에서는 이삭물수세미 추출물(EMS)의 항산화 효능과 항염증 효능을 분석하였다. 항산화 효능은 DPPH 라디칼 소거능과 환원력을 통해 산화적 스트레스를 통해 염증을 유발시킬 수 있는 ROS (Hong et al., 2020; Snezhkina et al., 2019)를 억제하는지 확인하였고, 항염증 효능은 염증 발현 인자인 LPS를 이용하여 RAW 264.7 대식세포에 염증을 유도한 뒤 pro-inflammatory cytokine (TNF-α, IL-1β)과 염증 매개체(NO, PGE₂)의 억제 및 TLR4/Myd88/NF-κB signaling pathway 발현 억제를 통해 확인하였다. 연구 결과, 항산화 효능에 있어서는 DPPH 라디칼 소거능과 Fe³⁺를 Fe²⁺로 환원시키는 환원력이 농도 의존적으로 증가함을 확인하였다. 무독성 상태에서 실험하기 위해 LPS와 EMS를 처리한 RAW 264.7 대식세포에서 90% 이상의 생존율을 나타내는 조건에서 실험을 진행하였다. LPS로 염증이 유도된 RAW 264.7 세포에서 EMS는 염증 매개 인자의 발현 및 생성 억제(iNOS에 의한 NO 생성 및 COX-2에 의한 PGE₂ 생성억제)와 pro-inflammatory cytokine (TNF-α 및 IL-1β)의 생성 또한 억제하였다. 특이적으로 COX-2에 의한 PGE₂ 생성 억제에서는 고농도에서 작용함을 확인하였고, IL-1β에서는 약한 억제력을 보였다. 이후 signaling pathway에서 염증 전사인자 경로를 확인하기 위하여 TLR4/MyD88의 활성을 확인하였고, EMS 처리에 따라 농도 의존적으로 억제되는 것을 확인하였다. 이에 따라 염증 초기 단계에서 NF-κB p65가 nuclear로 들어가는 것을 억제하는지 확인하기 위해 early time (LPS 처리 후 30, 60 min) 조건으로 nuclear에서 p65 인산화를 확인하였다. 그 결과, LPS 자극으로 인해 증가된 p65 인산화가 EMS에 의해 부분적으로 억제됨을 확인하였다. 이상의 결과를 통해 LPS로 염증이 유도된 RAW 264.7 대식세포에서 EMS가 COX-2에 의한 PGE₂ 생성 억제와 IL-1β의 생성에 있어 낮은 억제력을 가진 반면, iNOS에 의한 NO과 TNF-α 생성 및 TLR4/MyD88 singnaling pathway에 있어 강한 억제력을 가짐을 확인하였다. 결론적으로 EMS가 ROS를 제거하고 TLR4/MyD88/NF-κB signaling pathway를 억제함으로써 염증 인자들의 전사를 억제하고, 염증 인자 부분에서는 iNOS에 의한 NO 생성과 TNF-α 생성을 강하게 억제하여 RAW 264.7 대식세포에서 LPS로 자극된 염증을 억제하는 것으로 판단된다. 또한 TLR4/Myd88/NF-κB signaling pathway를 통한 pro-inflammatory cytokine과 염증 매개체와의 연관성에 대한 기초자료로 활용할 수 있는 근거 자료가 될 수 있을 것으로 생각된다.

• Journal of Microbiology and Biotechnology
• /
• 제33권9호
• /
• pp.1213-1227
• /
• 2023

Fetal growth restriction (FGR) is a prevalent obstetric condition. This study aimed to investigate the role of Toll-like receptor 9 (TLR9) in regulating the inflammatory response and gut microbiota structure in FGR. An FGR animal model was established in rats, and ODN1668 and hydroxychloroquine (HCQ) were administered. Changes in gut microbiota structure were assessed using 16S rRNA sequencing, and fecal microbiota transplantation (FMT) was conducted. HTR-8/Svneo cells were treated with ODN1668 and HCQ to evaluate cell growth. Histopathological analysis was performed, and relative factor levels were measured. The results showed that FGR rats exhibited elevated levels of TLR9 and myeloid differentiating primary response gene 88 (MyD88). In vitro experiments demonstrated that TLR9 inhibited trophoblast cell proliferation and invasion. TLR9 upregulated lipopolysaccharide (LPS), LPS-binding protein (LBP), interleukin (IL)-1β and tumor necrosis factor (TNF)-α while downregulating IL-10. TLR9 activated the TARF3-TBK1-IRF3 signaling pathway. In vivo experiments showed HCQ reduced inflammation in FGR rats, and the relative cytokine expression followed a similar trend to that observed in vitro. TLR9 stimulated neutrophil activation. HCQ in FGR rats resulted in changes in the abundance of Eubacterium_coprostanoligenes_group at the family level and the abundance of Eubacterium_coprostanoligenes_group and Bacteroides at the genus level. TLR9 and associated inflammatory factors were correlated with Bacteroides, Prevotella, Streptococcus, and Prevotellaceae_Ga6A1_group. FMT from FGR rats interfered with the therapeutic effects of HCQ. In conclusion, our findings suggest that TLR9 regulates the inflammatory response and gut microbiota structure in FGR, providing new insights into the pathogenesis of FGR and suggesting potential therapeutic interventions.

• 한국식품영양과학회지
• /
• 제42권10호
• /
• pp.1576-1584
• /
• 2013

이상의 결과를 종합해 볼 때, 높은 수준의 포도당 섭취는 공복혈당과 공복혈당면적을 높이고 혈중 인슐린 농도와 아티포넥틴의 수준을 낮추어 혈당조절 능력을 억제시켰다. 반면, 높은 수준의 과당 섭취는 인슐린을 요구하지 않는 과당대사의 특이성으로 인해 혈당조절에는 효과적으로 보인다. 그러나 고과당 섭취는 간 조직 및 혈중 중성지방의 농도를 높이고 염증조절복합체 구성단백질의 발현을 조절하여 전염증인자의 발현을 증가시켰다. 이는 간조직에 있어 과당이 포도당보다 높은 수준의 염증반응을 유도하여 NAFLD의 발병과 진행에 보다 유의적인 영향을 준다는 것을 보여준다. 본 연구의 제한점은 일상에서 과당이나 포도당을 단독으로 섭취하는 경우가 드물다는 점과 3주라는 짧은 중재기간에 의한 실험 결과라는 것이다. 앞으로의 연구는 단순당을 장기간 섭취했을 때 혈청과 간 조직을 포함한 다른 대사 관련조직에서 나타나는 변화에 초점을 맞출 필요가 있으며, 염증조절복합체가 염증인자의 발현을 증가시키는 기전을 구체화하는 것이 요구된다.

• Journal of Nutrition and Health
• /
• 제54권5호
• /
• pp.448-458
• /
• 2021

본 연구는 뽕나무 열매 착즙 분말 (MJ)이 지방세포 분화과정에서 염증에 관여하는 유전자 발현 및 miR-132/143 조절에 미치는 효과에 중점을 두고 조사하였다. MJ는 3T3-L1 지방세포 분화 동안 지질축적이 억제되었고 PPAR-γ, CEBP-α 및 aP2와 같은 지방형성 유전자 발현을 억제하였다. 또한 염증 조절 매개체인 TNF-α, IL-6, MCP-1 및 iNOS 유전자 발현이 MJ 처리에 의해 감소되었다. MJ의 지질 축적 억제 효과는 염증과 지방분화에 관여하는 miR-132/143의 발현 감소와 관련이 있음을 확인하였다. 따라서 MJ는 염증을 동반하는 비만 예방 및 치료에 도움이 될 수 있는 식품 소재로서 가능성이 있음을 시사하고 있다. 그러나 MJ의 주요 성분인 안토시아닌의 생체이용율은 1-2% 미만으로 추정되며 예상되는 표적 조직이나 혈류에서 미량 검출되는 것으로 알려져 있다 [33]. 이를 해결하기 위해서는 생체 내 동물실험을 통한 다각적인 분석이 향후 진행되어야 할 것으로 판단된다.