• 한방재활의학과학회지
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• 제29권2호
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• pp.101-113
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• 2019

Objectives Bogol-tang has clinically been used to protect joint cartilage and to treat osteoarthritis. Our objective was to study the protective effect of Bogol-tang extract (BGT) in functional impairment, behavioral disorders, cartilage loss and pathological changes in a monoiodoacetate (MIA)-induced murine osteoarthritis (OA) model and interleukin (IL)-$1{\beta}$ -treated primary rat chondrocytes. Methods Mouse knee joints were injected with MIA, a chemical that inhibits glycolysis and causes joint inflammation and matrix loss. MIA-OA induced mice orally administered BGT or acetaminophen (AAP) for 18 days by daily. Primary rat chondrocytes were pretreated with BGT or dexamethasone (DEX) and followed by co-incubation with IL-$1{\beta}$ (10 ng/mL). Results In MIA-OA mice model, BGT led to delayed response on hot plate analysis, and suppressed the cartilage loss and damages in joint tissues. BGT suppressed the elevated levels of inflammatory mediators, nitrite and $PGE_2$, the gene expression of matrix degrading enzymes, and extracellular-signal-regulated kinases 1/2 and c-JunN-terminal kinase phosphorylation in IL-$1{\beta}$-treated primary rat chondrocytes. Conclusions Our results suggest that BGT improve the knee joint function and delay the cartilage damages by anti-nociceptive, anti-inflammatory and ant-catabolic effects, which indicate BGT could be a potential candidate for osteoarthritis treatment.

• Journal of Microbiology and Biotechnology
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• 제33권7호
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• pp.864-874
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• 2023

Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

• 미생물학회지
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• 제45권2호
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• pp.91-98
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• 2009

닭의 전염성 F낭병 바이러스(IBDV)가 원인 바이러스인 전염성 F낭병은 전 세계 양계산업에 경제적으로 피해가 큰 중요한 질병이다. 이 연구의 목적은 닭에서 IBDV에 대한 방어면역을 유도하기 위한 in ovo 초회항원자극(priming)과 불활화백신에 의한 보강접종 방법에 항원보강제(adjuvant)로 chicken interleukin 6 (pcDNA-ChIL-6;plasmid encoding chicken interleukin-6)와 levamisole (LMS)의 효과를 조사하는 것이다. IBDV의 VP2, VP, VP3 protein을 암호화하는 유전자백신인 plasmid DNA vaccine (pcDNA-VP243) 단독 또는 pcDNA-ChIL-6 또는 LMS와 함께 18일령 부화란의 양막낭(amniotic sac)에 접종하고 부화한 1주령의 병아리에 불활화 IBD 백신을 근육 접종한 다음 3주령에 고병원성 IBDV인 SH/92 주로 공격 접종하고 10일 동안 관찰하였다. 백신하지 않은 공격접종 대조군이 100%의 폐사율을 보인 반면 pcDNA-VP243 단독 접종군과 pcDNA-VP243에 pcDNA-ChIL-6 또는 LMS를 첨가한 실험군은 모두 100%의 생존율을 나타내었다. 그러나 공격접종 후 F낭의 손상을 평가하기 위한 IBDV RNA의 검출, B/B ratio와 F낭의 병변지수(lesion score) 등을 분석한 결과 pcDNA-VP243에 pcDNA-ChIL-6 또는 LMS를 첨가한 실험군은 pcDNA-VP243 단독 접종군보다 향상된 방어효과를 나타내지 않았다. 이 실험결과는 유전자백신에 의한 in ovo 초회항원자극-불활화백신에 의한 보강접종법이 고병원성 IBDV로부터 닭을 보호하기 위한 효과적인 방법이었으나 pcDNA-ChIL-6 또는 LMS의 첨가로 인한 방어효과의 향상은 나타나지 않았다.

• IMMUNE NETWORK
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• 제24권1호
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• pp.1.1-1.6
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• 2024

IL-18 binding protein (IL-18BP) was originally discovered in 1999 while attempting to identify an IL-18 receptor ligand binding chain (also known as IL-18Rα) by subjecting concentrated human urine to an IL-18 ligand affinity column. The IL-18 ligand chromatography purified molecule was analyzed by protein microsequencing. The result revealed a novel 40 amino acid polypeptide. To isolate the complete open reading frame (ORF), various human and mouse cDNA libraries were screened using cDNA probe derived from the novel IL-18 affinity column bound molecule. The identified entire ORF gene was thought to be an IL-18Rα gene. However, IL-18BP has been proven to be a unique soluble antagonist that shares homology with a variety of viral proteins that are distinct from the IL-18Rα and IL-18Rβ chains. The IL-18BP cDNA was used to generate recombinant IL-18BP (rIL-18BP), which was indispensable for characterizing the role of IL-18BP in vitro and in vivo. Mammalian cell lines were used to produce rIL-18BP due to its glycosylation-dependent activity of IL-18BP (approximately 20 kDa). Various forms of rIL-18BP, intact, C-terminal his-tag, and Fc fusion proteins were produced for in vitro and in vivo experiments. Data showed potent neutralization of IL-18 activity, which seems promising for clinical application in immune diseases involving IL-18. However, it was a long journey from discovery to clinical use although there have been various clinical trials since IL-18BP was discovered in 1999. This review primarily covers the discovery of IL-18BP along with how basic research influences the clinical development of IL-18BP.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2002년도 춘계학술발표대회 발표논문초록집
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• pp.89-89
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• 2002

In this study, we examined transmission efficiency and expression level of the transgenes in the transgenic mice. The transgenic lines secreting a considerable amount of human lactoferrin(LF) thrombopoietin(TPO), interleukin-10(IL-10) into their milk were subjected to access the inheritance and maintenance of transgenic phenotype. They were bred through three generations. The transmission frequency for each generations(F9, F10, F11) of 3 lines was 38.03±10.43%(13/35), 48.33±3.76%(19/39) and 31.83±8.88%(9/28) in the LF line, 51.33±18.98%(20/38), 63.70±35.71%(12/20) and 29.57± 15.05%(8/26) in the TPO line, 38.27±17.74%(15/37), 47.47±29.88%(14/28) and 50.87±5.85%(14/28) in the IL-10 line, respectively. (omitted)

• 대한의생명과학회지
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• 제18권4호
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• pp.413-419
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• 2012

The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin-24 (IL-24), is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells. However, there have been few studies about its role in colorectal cancer. We performed immunohistochemical detection of MDA-7/IL-24 in 399 tissue samples from primary colorectal adenocarcinoma patients using a tissue microarray. Western blotting was then done to confirm the immunohistochemical observations. MDA-7/IL-24 immunoreactivity was observed in 116 (29.1%) of the 399 colorectal adenocarcinoma cases. Analysis of the MDA-7/IL-24 expression by Western blotting confirmed the immunohistochemical results. The tumors with a negative MDA-7/IL-24 expression more frequently showed poor differentiation (P=0004), lymph node metastasis (P=0.001), deep invasion (P=0.008) and high stage (P=0.001). A subset of colorectal adenocarcinoma revealed a decreased expression of MDA-7/IL-24, and this was associated with progressive pathologic features. These findings suggest that loss of MDA-7/IL-24 expression may play a role in tumor growth and progression of colorectal adenocarcinomas.

• Food Science and Biotechnology
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• 제18권3호
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• pp.706-711
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• 2009

Lysozyme was treated with digestive enzymes and the production of interleukin 8 (IL-8) was measured in Caco-2 cell with the peptides from lysozyme upon stimulating with lipopolysaccharide (LPS) to investigate the overall anti-inflammatory activity of lysozyme when it is in digestive tracts. Lysozyme reduced IL-8 production, and the peptides from pepsin hydrolysis of lysozyme had the similar effect. The products of trypsin digestion of lysozyme had no effect on the reduction of IL-8 production while those of pepsin-trypsin hydrolysis did. The effectiveness of lowering IL-8 production was not different by time of the peptide addition. When Caco-2 cells were pre-incubated with peptides for 24 hr, the reduction effects were observed from the peptides from pepsin hydrolysis, indicating that some of the peptides are still remaining in the cells. Therefore, it can be concluded that the IL-8 reduction effect of lysozyme against LPS still remained even after the pepsin and trypsin hydrolysis.

• Biomolecules & Therapeutics
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• 제18권2호
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• pp.135-144
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• 2010

The pro-oxidative and pro-inflammatory pathways in vascular endothelium have been implicated in the initiation and progression of atherosclerosis. In fact, inflammatory responses in vascular endothelium are primarily regulated through oxidative stress-mediated signaling pathways leading to overexpression of pro-inflammatory mediators. Enhanced expression of cytokines, chemokines and adhesion molecules in endothelial cells and their close interactions facilitate recruiting and adhering blood leukocytes to vessel wall, and subsequently stimulate transendothelial migration, which are thought to be critical early pathologic events in atherogenesis. Although interleukin-4 (IL-4) was traditionally considered as an anti-inflammatory cytokine, recent in vitro and in vivo studies have provided robust evidence that IL-4 exerts pro-inflammatory effects on vascular endothelium and may play a critical role in the development of atherosclerosis. The cellular and molecular mechanisms responsible for IL-4-induced atherosclerosis, however, remain largely unknown. The present review focuses on the distinct sources of IL-4-mediated reactive oxygen species (ROS) generation as well as the pivotal role of ROS in IL-4-induced vascular inflammation. These studies will provide novel insights into a clear delineation of the oxidative mechanisms of IL-4-mediated stimulation of vascular inflammation and subsequent development of atherosclerosis. It will also contribute to novel therapeutic approaches for atherosclerosis specifically targeted against pro-oxidative and pro-inflammatory pathways in vascular endothelium.

• 대한물리의학회지
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• 제5권4호
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• pp.551-558
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• 2010

연구목적 : 미세전류 자극이 아주반트로 류마티스 관절염을 유발한 실험동물의 염증반응과 통증에 미치는 효과를 알아보기 위하여 실험동물의 발허리발가락관절내 염증반응 정도를 나타내는 인터루킨-6(interleukin-6)의 발현과 핫플레이트(hot plate)를 이용한 발도피지연시를 측정하여 미세전류의 효과에 대하여 알아보고자 하는데 목적이 있다. 연구방법 : 실험동물은 무작위로 대조군(n=18)과 미세전류를 적용한 실험군(n=18)으로 구분하였고, 각 군당 6마리씩 1일군, 7일군, 14일군으로 배정하였다. 류마티스 관절염 유발후 1일, 7일, 14일에 모든 실험동물의 열통각 역치를 나타내는 발도피지연시와 발허리발가락관절내 인터루킨-6의 발현정도를 측정하였다. 각 집단 내의 기간에 따른 발도피지연시와 인터루킨-6의 면역반응성은 일원배치 분산분석을 실시하였고, 사후분석으로는 Duncan의 다중범위검정을 실시하였다. 실험군과 대조군을 비교하기 위하여 독립표본 t-test를 실시하였다. 연구결과 : 실험결과는 다음과 같다. 1) 아주반트 주사 1일후, 실험군과 대조군에서 인터루킨-6 면역반응성과 발도피지연시는 비슷한 양상을 보였다. 2) 인터루킨-6 면역반응성은 아주반트 주사 7일, 14일 후 대조군이 실험군보다 유의하게 증가되었다(p<.05). 3) 발도피지연시는 아주반트 주사 7일, 14일 후 실험군이 대조군보다 유의하게 증가되었다(p<.05). 결론 : 이상의 결과로부터, 미세전류 자극이 아주반트로 유발된 류마티스관절염 모델에서 활액 조직내 염증반응을 감소시키고 열통각역치는 증가되는 것을 알 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권6호
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• pp.475-480
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• 2014

We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the $IL-1{\alpha}$ gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of $IL-1{\alpha}$. Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and $IL-1{\alpha}$. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and $IL-1{\alpha}$ induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of $IL-1{\alpha}$. These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of $IL-1{\alpha}$ in monocytic cells via multiple signaling pathways.