• Tuberculosis and Respiratory Diseases
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• 제82권3호
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• pp.227-233
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• 2019

Background: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ${\geq}1%$ and ${\geq}50%$, respectively. The patients were significantly older in TPS ${\geq}1%$ group than in TPS <1% group ($64.83{\pm}9.38years$ vs. $61.73{\pm}10.78years$, p=0.014), not in TPS ${\geq}50%$ cutoff value ($64.69{\pm}9.39$ vs. $62.36{\pm}10.51$, p=0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ${\geq}1%$ (40.8% vs. 25.8%, p=0.020) and TPS ${\geq}50%$ groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ${\geq}1%$ (r=0.826; 95% confidence interval, 0.736-0.916). Conclusion: PD-L1 expression, defined as TPS ${\geq}1%$, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

• 생명과학회지
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• 제29권1호
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• pp.37-44
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• 2019

조릿대 잎은 항염, 해열, 이뇨작용 등의 약리효과를 가지고 있어 예로부터 전통의약에서 사용되어 왔다. 본 연구팀은 열수 추출한 후 남는 잔사로부터 식물화합물을 다량으로 함유한 잔사 추출물(PRE)을 제조하는 방법을 보고 바 있다. 본 연구는PRE의 고요산 혈증 저감소재로서 활용 가능성을 평가하기 위하여 수행하였다. Potassium oxonate(PO)로 유도한 고요산 혈증 생쥐 모델에서 PRE는 혈액 내의 요산, 요소 질소, 크레아틴 농도는 감소시켰고, 오줌 내의 요산과 크레아틴 농도는 증가하였다. 또한, PRE 투여한 고용산 혈증 생쥐에서 간 내 요산 농도와 xanthine oxidase 활성이 대조군에 비해 감소하였고, PRE는 PO에 의해 유도된 간 조직의 상해를 보호하였다. 이 결과는 PO로 유도된 고요산 혈증 생쥐에서 PRE는 항염증 및 세포보호 작용에 기인하는 것으로 판단된다. 부가적으로 PRE에 의한 신장조직에서 transcriptome의 반응 변화를 RNA 서열분석법으로 분석하였다. PRE는 주로 면역반응, 염증반응 및 대사과정에 관여하는 유전자의 발현에 영향을 미치는 것으로 나타났다. 본 연구 결과는 염증을 동반하는 고요산 혈증을 개선하는 소재로서의 PRE의 활용 가능성을 제시해 준다.

• 생명과학회지
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• 제31권2호
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• pp.237-247
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• 2021

신경염증(neuroinflammation)은 여러 신경 질환의 원인 인자로 확인되고있다. 중추 신경계에 발현되는 단백질 복합체인 NLRP3 인플라마좀은 미생물, 응집되고 잘못 접힌 단백질, ATP와 같은 광범위한 외인성 및 내인성 자극에 의해 감지되고 캐스페이즈-1(capase-1)을 활성화할 수 있다. 활성을 띠는 캐스페이즈-1은 IL-1b와 IL-18과 같은 염증성 사이토카인(pro-inflammatory cytokine)을 활성화시키고 급속한 세포사멸(파이롭토시스, pyroptosis)를 야기한다. IL-1b와 IL-18, 그리고 파이롭토시스를 통해 분비된 DAMPs은 다양한 신호 전달 경로를 통해 신경염증 반응을 유도하여 신경 손상을 유발한다. 따라서 NLRP3 인플라마좀은 신경염증으로 인한 여러 가지 신경질환 발병에 중요한 역할을 할 것으로 여겨진다. 본 리뷰 에서는 NLRP3 인플라마좀의 구조와 활성화에 대해 간략히 알아 보고 다양한 형태의 신경 질환에서 NLRP3 인플라마좀의 역할에 대해 논의하고자 한다.

• 대한화장품학회지
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• 제47권2호
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• pp.139-145
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• 2021

식물 유래 exosome-like nanovesicles (plant-derived exosome-like nanovesicles, PELNs)은 다양한 생물학적 활성을 포함하고 높은 생체 적합성을 가지고 있다. 인체 내에서 PELNs은 세포 분화 및 증식 조절에 영향을 미칠 수 있어 여러 산업 분야에서 응용이 가능하다. 하지만, PELNs의 피부 생리적 기능에 대한 연구는 포유류 nanovesicles에 비해 미미한 실정이다. 본 연구에서는 사과 열매로부터 캘러스를 유도하고 exosome-like nanovesicles (Exosome-like nanovesicles isolated from Malus domestica (apple) fruit callus, ACELNs)를 분리하여 피부 장벽 및 피부 노화 개선에 대한 연구를 수행하였다. ACELNs의 수율은 6.42 × 10⁹ particles/mL이였으며, 입자 사이즈는 100 ~ 200 nm 범위로 감지되었다. 인간 유래 피부세포인 HDF cells과 HaCaT cells에서 세포 증식을 유도하였으며, 세포 독성 억제 효과를 보였다. 각질형성능이 유의하게 증가했으며, mRNA levels에서 COL1A1과 FBN1 발현을 증가시켰다. 또한, UVA 조사된 HDF cells에 대한 collagen 합성을 촉진시켰다. 이러한 결과들은 ACELNs가 피부장벽 개선 및 피부노화를 방지할 수 있는 소재로서 활용하기 우수한 소재로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.207-216
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• 2021

Supplement of high-protein food plays an important role in improving the symptoms of malnutrition and the immune capacity of the body, but the association of high-protein diet and gut microbiota remained unaddressed. Here, we systematically analyzed the internal organs and gut microbiota in C57(WT) or PD-1H-depleted (KO) mice (T cells were activated) fed with pupae or feed for six weeks. We observed that the body weight gain in the mice fed with pupae increased less significantly than that of the feed group, while the villi and small intestine lengths in the pupa group were reduced compared with that of mice given feed. However, the average body weight of the KO mice increased compared with that of the WT mice fed with pupae or feed. Pupae increased the concentration of blood glucose in WT, but not in KO mice. Moreover, in the feed group, there was no difference in the weight of the internal organs between the WT and KO mice, but in the pupae-fed group, liver weight was decreased and spleen weight was increased compared with that of KO mice. The amounts/plural/amounts of Melainabacteria, Chloroflexi, and Armatimonadetes were specifically upregulated by pupae, and this upregulation was weakened or eliminated by PD-1H depletion. Some bacteria with high abundance in the feed-fed KO mice, such as Deferribacteres, Melainabacteria, Acidobacteria, Bacteroidetes, Spirochaetes and Verrucomicrobia, were decreased in pupae-fed KO mice, and Proteobacteria and Deinococcus were specifically enriched in pupae-fed KO mice. Bacteroidetes, Firmicutes and Akkermansia were associated with weight loss in the pupae-fed group while Lachnospiraceae and Anaerobiospirillum were related glucose metabolism and energy consumption. Based on high-throughput sequencing, we discovered that some gut bacteria specifically regulated the metabolism of a high-protein diet, and PD-1H deficiency improved life quality and sustained blood glucose. Moreover, PD-1H responses to high-protein diet through modulating the type and quantity of gut bacteria. These findings provide evidence about the association among gut microbiota, T cell activation (for PD-1H depletion) and high-protein diet metabolism, have important theoretical significance for nutrition and health research.

• Animal Bioscience
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• 제35권7호
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• pp.964-974
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• 2022

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry and economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for studies on HPAIV resistance. Therefore, in this study, we investigated gene expression related to the mitogen-activated protein kinase (MAPK) signaling pathway by comparing non-infected, HPAI-infected resistant, and susceptible Ri chicken lines. Methods: Resistant (Mx/A; BF2/B21) and susceptible Ri chickens (Mx/G; BF2/B13) were selected by genotyping the Mx and BF2 genes. Then, the tracheal tissues of non-infected and HPAIV H5N1 infected chickens were collected for RNA sequencing. Results: A gene set overlapping test between the analyzed differentially expressed genes (DEGs) and functionally categorized genes was performed, including biological processes of the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. A total of 1,794 DEGs were observed between control and H5N1-infected resistant Ri chickens, 432 DEGs between control and infected susceptible Ri chickens, and 1,202 DEGs between infected susceptible and infected resistant Ri chickens. The expression levels of MAPK signaling pathway-related genes (including MyD88, NF-κB, AP-1, c-fos, Jun, JunD, MAX, c-Myc), cytokines (IL-1β, IL-6, IL-8), type I interferons (IFN-α, IFN-β), and IFN-stimulated genes (Mx1, CCL19, OASL, and PRK) were higher in H5N1-infected than in non-infected resistant Ri chickens. MyD88, Jun, JunD, MAX, cytokines, chemokines, IFNs, and IFN-stimulated expressed genes were higher in resistant-infected than in susceptible-infected Ri chickens. Conclusion: Resistant Ri chickens showed higher antiviral activity compared to susceptible Ri chickens, and H5N1-infected resistant Ri chickens had immune responses and antiviral activity (cytokines, chemokines, interferons, and IFN-stimulated genes), which may have been induced through the MAPK signaling pathway in response to H5N1 infection.

• BMB Reports
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• 제55권6호
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• pp.275-280
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• 2022

The treatment of atopic dermatitis (AD) is challenging due to its complex etiology. From epidermal disruption to chronic inflammation, various cells and inflammatory pathways contribute to the progression of AD. As with immunosuppressants, general inhibition of inflammatory pathways can be effective, but this approach is not suitable for long-term treatment due to its side effects. This study aimed to identify a plant extract (PE) with anti-inflammatory effects on multiple cell types involved in AD development and provide relevant mechanistic evidence. Degranulation was measured in RBL-2H3 cells to screen 30 PEs native to South Korea. To investigate the anti-inflammatory effects of Parasenecio auriculatus var. matsumurana Nakai extract (PAE) in AD, production of cytokines and nitric oxide, activation status of FcεRI and TLR4 signaling, cell-cell junction, and cell viability were evaluated using qRT-PCR, western blotting, confocal microscopy, Griess system, and an MTT assay in RBL-2H3, HEK293, RAW264.7, and HaCaT cells. For in vivo experiments, a DNCBinduced AD mouse model was constructed, and hematoxylin and eosin, periodic acid-Schiff, toluidine blue, and F4/80-staining were performed. The chemical constituents of PAE were analyzed by HPLC-MS. By measuring the anti-degranulation effects of 30 PEs in RBL-2H3 cells, we found that Paeonia lactiflora Pall., PA, and Rehmannia glutinosa (Gaertn.) Libosch. ex Steud. show an inhibitory activity of more than 50%. Of these, PAE most dramatically and consistently suppressed cytokine expression, including IL-4, IL-9, IL-13, and TNF-α. PAE potently inhibited FcεRI signaling, which mechanistically supports its basophil-stabilizing effects, and PAE downregulated cytokines and NO production in macrophages via perturbation of toll-like receptor signaling. Moreover, PAE suppressed cytokine production in keratinocytes and upregulated the expression of tight junction molecules ZO-1 and occludin. In a DNCB-induced AD mouse model, the topical application of PAE significantly improved atopic index scores, immune cell infiltration, cytokine expression, abnormal activation of signaling molecules in FcεRI and TLR signaling, and damaged skin structure compared with dexamethasone. The anti-inflammatory effect of PAE was mainly due to integerrimine. Our findings suggest that PAE could potently inhibit multi-inflammatory cells involved in AD development, synergistically block the propagation of inflammatory responses, and thus alleviate AD symptoms.

• Animal Bioscience
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• 제35권3호
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• pp.367-376
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• 2022

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry as well as the economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for HPAIV resistance. Therefore, in this study, we investigated gene expression related to cytokine-cytokine receptor interactions by comparing resistant and susceptible Ri chicken lines for avian influenza virus infection. Methods: Ri chickens of resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) lines were selected by genotyping the Mx dynamin like GTPase (Mx) and major histocompatibility complex class I antigen BF2 genes. These chickens were then infected with influenza A virus subtype H5N1, and their lung tissues were collected for RNA sequencing. Results: In total, 972 differentially expressed genes (DEGs) were observed between resistant and susceptible Ri chickens, according to the gene ontology and Kyoto encyclopedia of genes and genomes pathways. In particular, DEGs associated with cytokine-cytokine receptor interactions were most abundant. The expression levels of cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and IL-18), chemokines (C-C Motif chemokine ligand 4 [CCL4] and CCL17), interferons (IFN-γ), and IFN-stimulated genes (Mx1, CCL19, 2'-5'-oligoadenylate synthase-like, and protein kinase R) were higher in H5N1-resistant chickens than in H5N1-susceptible chickens. Conclusion: Resistant chickens show stronger immune responses and antiviral activity (cytokines, chemokines, and IFN-stimulated genes) than those of susceptible chickens against HPAIV infection.

• Clinical and Experimental Reproductive Medicine
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• 제50권1호
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• pp.44-52
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• 2023

Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.

• 대한임상검사과학회지
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• 제54권1호
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• pp.38-48
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• 2022

Carcinoembryonic antigen (CEA)는 다양한 종양에서 발현되는 자가 항원으로 면역치료에서 강력한 표지 인자이며 면역치료를 위한 표적 종양항원으로 널리 알려져 있다. 그러나 수지상세포 단독 치료는 동물모델에서 종양의 발생을 억제하는 데 효과가 있지만 이미 확립된 종양을 제거하는 데는 한계가 있다. 본 연구에서는 항종양 면역 효과를 증가시키기 위하여 화학치료제인 cyclophosphamide (CYP)와 종양 특이 면역치료법인 수지상세포 백신의 병합치료 효과를 CEA를 발현하는 마우스 종양 모델에서 검증하였다. 종양세포 주입 후 2일 소종양군과 10일 대종양군에서 CYP의 항종양 효과를 비교한 결과, 소종양군에서는 100 mg/kg에서 뚜렷한 종양 성장의 억제 효과가 관찰되었지만 대종양군에서는 약한 억제 효과가 관찰되어 본 연구에서는 대종양군을 병합치료의 적합한 모델로 설정하였다. CYP 와 수지상세포 백신의 병합치료(화학면역치료) 시 종양항원 특이 면역반응이 증가되었을 뿐만 아니라 상승적인 항종양 효과가 나타났다. 또한 CYP 치료에서 나타나는 체중 감소 및 조절 T세포와 골수유래 억제세포의 증가에 의한 면역억제는 화학면역치료에 의해 개선되었다. 항원 특이 면역치료를 병합한 화학면역치료가 화학치료의 부작용을 감소시키고 항종양 효과를 증가시킬 수 있는 치료 전략이 될 수 있을 것이다.