• Molecules and Cells
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• 제44권5호
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• pp.301-309
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• 2021

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. ILCs can be categorized into three groups on the basis of the transcription factors that direct their functions and the cytokines they produce. Notably, these functions parallel the effector functions of T lymphocytes. ILCs play a frontline role in host defense and tissue homeostasis by responding rapidly to environmental factors, conducting effector responses in a tissue-specific manner, and interacting with hematopoietic and non-hematopoietic cells throughout the body. Moreover, recent studies reveal that ILCs are involved in development of various inflammatory diseases, such as respiratory diseases, autoimmune diseases, or cancer. In this review, we discuss the recent findings regarding the biology of ILCs in health and inflammatory diseases.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.190-191
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• 2003

Endometriosis is classically defined as the growth of endometrial glands and stroma at extrauterine sites. Although it is a common gynecological problem accompanied by chronic pelvic pain, infertility, and adhesion formation, the etiology of this disease is unknown. Endometriosis pathogenesis may involve endocrine and immune dysfunction since uterine endometrial growth is regulated by sex hormones in concert with bioactive mediators produced by uterine immune and endocrine cells. Thus, exposure to environmental toxicants disrupting endocrine and immune responses potentially affect the development and progression of endometriosis.

• IMMUNE NETWORK
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• 제16권4호
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• pp.201-210
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• 2016

Allergic inflammation requires the orchestration of altered gene expression in the target tissue and in the infiltrating immune cells. The transcription factor STAT6 is critical in activating cytokine gene expression and cytokine signaling both in the immune cells and in target tissue cells including airway epithelia, keratinocytes and esophageal epithelial cells. STAT6 is activated by the cytokines IL-4 and IL-13 to mediate the pathogenesis of allergic disorders such as asthma, atopic dermatitis, food allergy and eosinophilic esophagitis (EoE). In this review, we summarize the role of STAT6 in allergic diseases, its interaction with the co-factor PARP14 and the molecular mechanisms by which STAT6 and PARP14 regulate gene transcription.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3131-3138
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• 2016

Several studies have addressed the possible role of hepatitis C virus genotype-4 (HCV GT4) in apoptosis. However, this still not fully understood. In the current study a re-constructed clone of E1/E2 polyprotein region of the HCV GT4 was transfected into the Huh7 cell line and a human apoptotic PCR array of 84 genes was used to investigate its possible significance for apoptosis. Out of the 84 genes, only 35 showed significant differential expression, 12 genes being up-regulated and 23 down-regulated. The highest-up regulated genes were APAF1 (apoptotic peptidase-activating factor 1), BID (BH3 interacting domain death agonist) and BCL 10 (B-cell CLL/lymphoma protein 10) with fold regulation of 33.2, 30.1 and 18.9, respectively. The most down-regulated were FAS (TNF receptor super family), TNFRSF10B (tumor necrosis factor receptor super-family member 10b) and FADD (FAS-associated death domain) with fold regulation of -30.2, -27.7 and -14.9, respectively. These results suggest that the E1/E2 proteins may be involved in HCV-induced pathogenesis by modulating apoptosis through the induction of the intrinsic apoptosis pathway and disruption of the BCL2 gene family.

• Animal cells and systems
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• 제13권4호
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• pp.391-397
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• 2009

The house dust mite (Dermatophagoides pteronissinus) is an important factor in triggering allergic diseases. The function of eosinophils, particularly in the production of cytokine or chemokine, is critical in understanding the pathogenesis of inflammatory diseases. In this study, we examined whether D. pteronissinus extract (DpE) induces the expression of monocyte chemotactic protein 1 (MCP-1)/CCL2, IL-8/CXCL8, and IL-6 that mediate in the infiltration and activation of immune cells and in its signaling mechanism in the human eosinophilic cell line, EoL-1. DpE increased the mRNA and protein expression of MCP-1, IL-8, and IL-6 in a time- and dose-dependent course in EoL-1 cells. In our experiments using signal-specific inhibitors, we found that the increased expression of MCP-1, IL-8, and IL-6 due to DpE is associated with Src family tyrosine kinase and protein kinase C $\delta$ (PKC $\delta$). In addition, the activation of extracellular signal-regulated kinase (ERK) is required for MCP-1 and IL-8 expression while p38 mitogen-activated protein kinase (MAPK) is involved in IL-6 expression. DpE induced the phosphorylation of ERK and p38 MAPK. PP2, an inhibitor of Src family tyrosine kinase, and rottlerin, an inhibitor of PKC $\delta$, blocked the activation of ERK and p38 MAPK. DpE induces the activation of ERK and p38 MAPK via Src family tyrosine kinase and PKC $\delta$ for MCP-1, IL-8, or IL-6 production. Increased cytokine release due to the house dust mite and the characterization of its signal transduction may be valuable in understanding the eosinophil-related pathogenic mechanism of inflammatory diseases.

• Journal of Gastric Cancer
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• 제3권2호
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• pp.84-87
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• 2003

Purpose: Evidence exists that dysregulation of Bcl-2 family members is involved in the pathogenesis of cancer development. The aim of this study was to explore whether the somatic mutation of proapoptotic Bcl-2 member genes, one of the mechanisms that prolong the survival of cancer cells, is involved in gastric carcinogenesis. Materials and Methods: In the current study, to detect somatic mutations of the DNA sequences encoding the Bcl-2 homology 3 (BH3) domain of the human BAD, BIM, BIK, and Bcl-G genes in 60 advanced gastric adenocarcinomas, we used the polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing. Results: The SSCP analysis revealed no mutations in the coding regions of the BH3 domain in the cancers. Conclusion: The data presented here indicate that proapoptotic Bcl-2 member genes, BAD, BIM, BIK, and Bcl-G, may not be mutated in human gastric carcinomas and suggest that these genes might be altered by mechanisms other mechanisms somatic mutation.

• BMB Reports
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• 제35권5호
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• pp.524-531
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• 2002

Thrombotic thrombocytopenic purpura (TTP) is characterized by widespread platelet thrombi in arterioles and capillaries. Unusually large or multimeric von Willebrand factor, as well as one or ore platelet-agglutinating factors, have been implicated in the pathogenesis of TTP. But, the actual mechanisms of platelet agglutination have not been satisfactorily explained. Recent studies suggested the 37-kDa platelet-agglutinating protein (PAP) p37 to be partially responsible for the formation of platelet thrombi in patients with TTP. We studied mobility in SDS-PAGE, the sequence of N-terminal amino acid residues, DNA and antigenic characteristics of PAP p37, which might be related to the pathogenesis of TTP. PAP p37 was purified from the plasma of a 31-year-old male Korean patient with acute TTP. The findings are as follows: (1) We compared PAP p37 with thrombin through the use of SDS-PAGE, either with or without $\beta$-mercaptoethanol. PAP p37 did not appear to be cleaved between the A- and B-chains of prethrombin 2. However, thrombin did cleave between those of prethrombin 2, but linked with disulfide bridge. (2) N-terminal 21 amino acid sequence of PAP p37 was T-F-G-S-G-E-A-D-X-G-L-R-P-L-F-E-K-K-S-L-E. It appeared to be identical to that of 285-305 amino acid residues of human prothrombin (prethrombin 2). (3) No prothrombin gene DNA mutation was revealed. (4). The antigenicity of PAP p37 was similar to thrombin, which was a result of the competitive binding against the anti-thrombin antibody. With these results, we conclude that PAP p37 has similar characteristics to prethrombin2.

• Journal of Microbiology and Biotechnology
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• 제34권5호
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• pp.1059-1072
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• 2024

Oxidative stress is a key factor in the pathogenesis of benign prostatic hyperplasia (BPH) that leads to inflammation. This study aimed to evaluate the ameliorative effects of Salvia miltiorrhiza Bunge extract (HLT-101) on BPH through the regulation of oxidative stress and inflammation. A testosterone propionate (TP)-induced BPH rat model was orally administered HLT-101 (20, 40, or 80 mg/kg), and its effects on oxidative stress- and inflammation-related gene expression were examined. Further, HLT-101 was assessed for its effect on reactive oxygen species (ROS) levels and Nrf-2/HO-1 signaling pathways in BPH-1 cells. HLT-101 decreased testosterone-induced excessive free radical production and inflammatory factor activation. Moreover, HLT-101 treatment significantly decreased the intracellular ROS level in the TNF-α and IFN-γ treated BPH-1 cells through the activation of Nrf-2. In addition, HLT-101 treatment inhibited the NF-κB pathway and androgen receptor (AR) signaling, which is highly linked to the pathogenesis of BPH. Therefore, HLT-101 has the potential to be an effective treatment reagent for BPH because of its ability to reduce inflammation and oxidative stress via Nrf-2/HO-1 signaling.

• Journal of Oral Medicine and Pain
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• 제30권3호
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• pp.301-317
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• 2005

전 세계적으로 구강암의 빈도는 점점 증가 추세이며, 특히 한국인의 있어 혀(tongue)는 구강암이 가장 호발하는 장소이다. 구강암은 발암 단계에서부터 과증식 병소(hyperplastic lesion), 이형성(dysplasia) 및 상피내암(carcinoma in situ) 을 거쳐 악성 암종으로 발전하는 다단계 발암과정을 보이며, 분자 생물학적 변이가 구강암을 진행시킴이 널리 알려져 있다. 또한, 구강암은 일반적으로 암세포의 증식 및 고사(apoptosis)의 억제가 중요한 역할을 하고 있다 알려져 있다. 그리고, Bcl-2 family 는 세포 고사에 주요한 역할을 하고 있음이 알려져 있다. 그러나, 이들과 관련한 구강암 발생과정의 변화에 대해서는 널리 연구된 바가 없다. 본 연구는 백서에서 발암 물질인 4-NQO로 구강암을 유도시키고, 구강암 발생 다단계별로 Bcl-2 family의 mRNA 변화를 RT-PCR을 이용해 살펴보았다. Bcl-2 family는 크게 3군, 즉 1) anti-apoptotic, 2) pro-apoptotic, 그리고 3) BH3 only protein으로 분류할 수 있으며, 본 연구에서 anti-apoptotic molecules인 Bcl-w는 모든 군에서 발현이 감소되었으며, Bcl-2는 발현이 증가 되었다. pro-apoptotic molecules에서는 Bad가 제 3군 (편평세포암종)에서 발현이 증가 되었고, 나머지는 감소하였다. BH-3 only protein에서는 Bmf가 제 2군에서, BBC3가 제 3군에서 발현이 증가하였고, 나머지는 모든 군에서 감소하였다. 결론적으로, 4-NQO로 유도된 백서의 발암단계에서, Bcl-2 family의 mRNA 양상은 다양하게 관찰되었으나, Bad 및 BBC3 mRNA가 제 3군에서, Bmf mRNA가 제 2군에서의 발현이 특별함을 알 수 있어, 다단계 발암과정에서의 구강암을 진단하는데 유용하리라 사료된다.

• Animal cells and systems
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• 제15권4호
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• pp.301-309
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• 2011

Charcot-Marie-Tooth disease (CMT) is clinically heterogeneous hereditary motor and sensory neuropathies with genetic heterogeneity, age-dependent penetrance, and variable expressivity. Rare copy number variations by nonrecurrent rearrangements have recently been suggested to be associated with Charcot-Marie-Tooth 1A (CMT1A) neuropathy. In our previous study, we found three Korean CMT1A families with rare copy number variations (CNVs) on 17p12 by nonrecurrent rearrangement. Careful clinical examinations were performed in all the affected individuals with rare CNVs (n=19), which may be the first full study of a subject from a large CMT1A family with nonrecurrent rearrangement. The clinical phenotype showed no significant difference compared with common CMT1A patients, but with variable phenotypes. In particular, a broad intrafamilial phenotypic spectrum was observed within the same family, which may suggest the existence of a genetic modifier. This study may broaden the understanding of the role of CNVs in the pathogenesis of CMT.