• 한국동물생명공학회지
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• 제35권4호
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• pp.297-306
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• 2020

The aims of the present study were to confirm that regulation of the PA and environment via TGF-β regulation of sperm by Percoll-separated in porcine uterine epithelial cells. And, it was performed to identify the cytokines (TGF-β1, 2 and 3, TGF-β receptor1 and 2; interleukin, IL-6, IL-8) and PA-related genes (urokinase-PA, uPA; tissue-PA, tPA; PA inhibitor, PAI; uPA-receptor, uPAR) by spermatozoa. The experiment used porcine uterus epithelial cells (pUECs) and uterine tissue epithelial cells, Boar sperm were separated by discontinuous Percoll density gradient (45/90%), and tissues were co-incubated with spermatozoa, followed by real-time PCR. PA activity was measured of sperm by discontinuous Percoll density gradient (45/90%) for 24 hours. To measure viability and acrosome damage of sperm double stained propidium iodide (PI) and SYBR-14 or FITC-PNA were used. In results, binding ratio of Percoll-separated sperm was found no differences, but sperms isolated from 90% Percoll layer reduced PA activity (p < 0.05). when co-cultured sperm selected Percoll in porcine uterus tissues epithelial cells, 90% layer sperm increased TGF-β R1, contrastively tPA and PAI-1 in comparison with control (p < 0.05). 45% sperm was decreased the expression of uPA (p < 0.05). TGF-β decreased PA activity in the supernatant collected from pUECs (p < 0.05). Especially, The group including uPA, PAI-1 were induce sperm intact, while it was reduced in sperm damage when compared to control (p < 0.05). Also, there was no significant difference group of tPA and tPA+I in the dead sperm and acrosome damage compared to control. The expression of tPA and PAI showed a common response. Percoll-separated spermatozoa in 90% layer reduced tPA and IL-related gene mRNA expression. Thus, Percoll-sparated sperm in 90% layer show that it can suppress inflammation through increased expression of TGF-β and downregulation of PA and IL in epithelial cells compared to 45% layer Percoll.

• Clinical and Experimental Pediatrics
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• 제60권7호
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• pp.208-215
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• 2017

Purpose: Activation of Toll-like receptor 2 (TLR2) present on circulating monocytes in patients with Kawasaki disease (KD) can lead to the production of proinflammatory cytokines and interleukin-10 (IL-10). We aimed to determine the association of the frequency of circulating TLR2+/ CD14+ monocytes (FTLR2%) with the outcomes of KD, as well as to compare FTLR2% to the usefulness of sIL-10. Methods: The FTLR2% in patients with KD was measured by flow cytometry. Serum levels of IL-10 (sIL-10) were determined in 31 patients with KD before the initial treatment with intravenous immunoglobulin (IVIG) and in 21 febrile controls by using enzyme-linked immunosorbent assay. Patients were classified as having coronary artery lesions (CALs) based on the maximal internal diameters of the proximal right coronary artery and proximal left anterior descending coronary artery one month after the initial diagnosis. Results: We found that FTLR2% greater than 92.62% predicted CALs with 80% sensitivity and 68.4% specificity, whereas FTLR2% more than 94.61% predicted IVIG resistance with 66.7% sensitivity and 71.4% specificity. Moreover, sIL-10 more than 15.52 pg/mL predicted CALs and IVIG resistance with 40% and 66.7% sensitivity, respectively, and 73.7% and 76.2% specificity, respectively. Conclusion: We showed that measuring FTLR2% before the initial treatment could be useful in predicting CAL development with better sensitivity than sIL-10 and with results comparable to sIL-10 results for the prediction of IVIG resistance in patients with KD. However, further studies are necessary to validate FTLR2% as a marker of prognosis and severity of KD.

• Journal of Ginseng Research
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• 제47권2호
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• pp.291-301
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• 2023

Introduction: Non-small cell lung cancer (NSCLC) patients are particularly vulnerable to the Coronavirus Disease-2019 (COVID-19). Currently, no anti-NSCLC/COVID-19 treatment options are available. As ginsenoside Rg3 is beneficial to NSCLC patients and has been identified as an entry inhibitor of the virus, this study aims to explore underlying pharmacological mechanisms of ginsenoside Rg3 for the treatment of NSCLC patients with COVID-19. Methods: Based on a large-scale data mining and systemic biological analysis, this study investigated target genes, biological processes, pharmacological mechanisms, and underlying immune implications of ginsenoside Rg3 for NSCLC patients with COVID-19. Results: An important gene set containing 26 target genes was built. Target genes with significant prognostic value were identified, including baculoviral IAP repeat containing 5 (BIRC5), carbonic anhydrase 9 (CA9), endothelin receptor type B (EDNRB), glucagon receptor (GCGR), interleukin 2 (IL2), peptidyl arginine deiminase 4 (PADI4), and solute carrier organic anion transporter family member 1B1 (SLCO1B1). The expression of target genes was significantly correlated with the infiltration level of macrophages, eosinophils, natural killer cells, and T lymphocytes. Ginsenoside Rg3 may benefit NSCLC patients with COVID-19 by regulating signaling pathways primarily involved in anti-inflammation, immunomodulation, cell cycle, cell fate, carcinogenesis, and hemodynamics. Conclusions: This study provided a comprehensive strategy for drug discovery in NSCLC and COVID-19 based on systemic biology approaches. Ginsenoside Rg3 may be a prospective drug for NSCLC patients with COVID-19. Future studies are needed to determine the value of ginsenoside Rg3 for NSCLC patients with COVID-19.

• Childhood Kidney Diseases
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• 제9권2호
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• pp.175-182
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• 2005

목 적 : IL-1ra는 항염증반응을 가지고 있는 인자로서 IL-1 수용체와 결합하여, IL-l$\alpha$와 IL-1$\beta$의 결합을 경쟁적으로 억제시킴으로써, IL-1에 의해 매개되는 다양한 질환에서 중요한 내인성 조절인자로 작용한다. 이 유전자의 intron 2 부위에 86 bp 크기를 가지는 tandem repeat 에 의한 유전자 다형성이 존재하는데, 다양한 자가면역질환에서는 allele 2형의 빈도가 정상 인구군에 비해 유의하게 높다는 사실이 밝혀져 있다. 이에 저자들은 Henoch-$Sch{\ddot{o}}nlein$ Purpura 환자들을 대상으로 IL-1ra 유전자의 variable number tandem repeats(VNTR) 다형성을 검사하여 정상 대조군과 비교하였으며, 신장 침범 여부 및 중증의 경과에 $IL1RN^{*}2$가 어떤 영향을 미치는 지를 조사하였다. 방 법.: 1998년 1월부터 2002년 12월까지 부산 백병원 .소아과를 방문하여 Henoch-$IL1RN^{*}2$ purpura로 진단된 74명의 환자와 정상 대조군 43명을 대상으로 하였다. EDTA 처리된 전혈에서 상품화된 DNA 추출키트($QIAamp^{\circledR}$ DNA Blood Mini kit, Quiagen, USA)를 사용하여 DNA를 추출하였다. IL-1ra 유전자 다형성(polymorphysm)은 86 bp의 2, 3, 4, 5번의 반복횟수에 따라 각각 240 bp, 325 bp, 410 bp 또는 500 bp 크기의 밴드를 확인하여 결정하였다. 결 과 : HSP 환자군과 정상 대조군 모두에서 $IL1RN^{*}1$의 allele 빈도가 각각 $93.9\%,\;93.2\%$로 가장 높았으며, carriage rate도 각각 $98.6\%,\;97.9\%$로 가장 높았다. $IL1RN^{*}2$의 allele 빈도는 HSP 군에서 4.7$\%$로 대조군의 2.5$\%$에 비해 높았으나, 통계적으로 유의하지 않았다(P=0.794). Carriage rate도 HSP군에서 8.1$\%$로 대조군의 6.8$\%$에 비해 높았으나, 통계적으로 유의하지 않았다(P=0.915). $IL1RN^{*}2$의 allele 빈도는 신장 침범군에서 6.3$\%$로 비침범군의 2.9$\%$에 비해 높게 나타났으나 통계적으로 유의하지 않았다(P=0.356). Carriage rate는 신장 침범군에서 10.0$\%$, 비침범군에서 5.9$\%$였으며, 양군 사이에는 유의한 차이가 관찰되지 않았다(P=0.523). 24시간 채집뇨에서 측정한 총단백량이 1,000 mg 이상이었던 경우가 13명이었는데, 이들의 allele형은 $IL1RN^{*}1$이 11명이었으며, $IL1RN^{*}2와\;IL1RN^{*}4$형이 각각 1명씩 있었다. 마지막 추적관찰 시점까지 단백뇨가 지속되었던 환자는 4명이었으며 이들은 모두 $IL1RN^{*}1$형 이었다. 결 론 : HSP 환자군과 정상 대조군 모두에서 $IL1RN^{*}1$의 allele 빈도와 carriage rate가 가장 높았다. $IL1RN^{*}2$ allele 빈도와 carriage rate는 HSP 환자군에서 대조군과 비교하여 유의한 차이가 관찰되지 않았다. 또한 HSP 환자군에서도 $IL1RN^{*}2$ allele 빈도와 carriage rate는 신장 침범의 정도와도 유의한 관련성이 발견되지 않았다.

• 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.

• Childhood Kidney Diseases
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• 제3권1호
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• pp.27-34
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• 1999

목 적 : 가능한 교란인자들, 즉 연령, 단백뇨, 스테로이드 사용 등의 영향이 배제된 조건에서 소아의 신증후군, 또는 그 중의 어떤 특성이 혈청이나 요의 용해성 인터루킨-2수용체 (sIL-2R)에 영향을 주는지를 알기 위해 이 연구를 시행하였다. 방 법 : 소아의 일차성 신증후군 중 임상적 혹은 병리소견으로 미세변화형 신증후군으로 진단되거나 병리소견상 초점성 분절성 사구체경화증으로 진단된 환아를 대상으로 이들을 연령 (0-l세, 2-4세, 5세 이상), 단백뇨 및 스테로이드 사용 여부 (PU+Tx-, PU+Tx+, PU-Tx+, PU-Tx-)로 구분하였다. 이들과 대조군의 혈청, 요에서 ELISA법으로 각각 sIL-2R를 정량하고, 요에서는 크레아티닌치도 측정하였다. 각 군의 혈청 sIL-2R치와 요 sIL-2R/크레아티닌 비를 계산하여 비교하였다. 결 과 : 혈청 sIL-2R는 환자와 대조군에서 도두 연령이 어릴수록 높았고, 신증후군에서 대조군보다 높지 않았다. 환자군 중에서 재발한 경우에는 높고 스테로이드 투여 시에는 낮은 경향을 보였다. 요 sIL-2R/크레아티닌 비는 특히 단백뇨가 있을 때 연령이 어릴수록 높았고 (P=0.01), 혈청 치와 마찬가지로 재발과 스테로이드의 영향을 받았다. 혈청 sIL-2R치와 요 sIL-2R/크레아티닌 비는 신 병리소견, 스테로이드 반응도에 따른 차이를 보이지 않았다 (P>0.05). 결 론 : 혈청 sIL-2R치는 연령에 따른 차이가 크고, 신증후군에서 대조군에 비해 높지 않았으나, 재발상태의 환자는 완해 상태의 환자보다 높았고, 스테로이드를 투여할 때에 낮았다. 요 sIL-2R/크레아티닌 비는 특히 단백뇨가 있을 때 혈청 sIL-2R치를 잘 반영하였다.

• International Journal of Oral Biology
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• 제40권1호
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• pp.11-17
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• 2015

The gingival epithelium of the oral cavity is constantly exposed to exogenous stimuli such as bacterial toxins, allergens, and thermal changes. These exogenous stimuli are resisted by innate host defense in gingival epithelial cells. However, it is unclear exactly how the exogenous stimuli affect detrimentally on the human gingival epithelial cells. Here, we investigated whether the allergen, such as house dust mite (HDM) extract, is linked to $Ca^{2+}$ signaling and proinflammatory cytokine expression in primary cultured human gingival epithelial cells. HDM extract induced an increase in intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in a dose-dependent manner. Extracellular $Ca^{2+}$ depletion did not affected on the HDM extract-induced increase in $[Ca^{2+}]_i$. The HDM extract-induced increase in $[Ca^{2+}]_i$ was abolished by the treatment with U73122 and 2-APB, which are inhibitors of phospholipase C (PLC) and inositol 1,4,5-trisphosphate ($IP_3$) receptor. Moreover, HDM extract induced the mRNA expression of pro-inflammatory cytokine, interleukin (IL)-8. These results suggest that HDM extract triggers $PLC/IP_3$-dependent $Ca^{2+}$ signaling and IL-8 mRNA expression in primary cultured human gingival epithelial cells.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.383-389
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• 2017

Dexmedetomidine is an ${\alpha}2$-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of $1{\mu}g/kg$ load dose, followed by $0.05{\mu}g/kg/min$ infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-$1{\beta}$, interleukin-6 and tumor nevrosis factor-${\alpha}$ as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-${\kappa}Bp65$, inhibitor of ${\kappa}B{\alpha}$ and phosphorylated of ${\kappa}B{\alpha}$ in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-${\kappa}B$ pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

• 대한의생명과학회지
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• 제13권2호
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• pp.149-152
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• 2007

Mast cells play important roles in immune-related diseases, in particular, allergic diseases. Although 9-cis retinoic acid (9CRA) has been known as an immune regulator, its function in mast cells is not characterized well. In a previous paper, we demonstrated that 9CRA differentially decreases both CCR2 expression and the MCP-1-induced chemotactic activity of the human mast cell line, HMC-1 cells. In the present study, we examined the effects of 9CRA on the migration and expressions of inflammatory cytokines in HMC-1 cells. It was found that 9CRA significantly inhibited the migration of HMC-1 cells in response to stem cell factor (P<0.01), and it had no effect on the mRNA and protein expression of c-kit, a receptor binding to SCF. We further investigated the alternation of inflammatory cytokine expression and identified that 9CRA blocked the mRNA and protein expressions of Th2 cytokines such as interleukin (IL)-4 and IL-5. Taken together, our results demonstrate that 9CRA blocks SCF-induced cell movement and the protein secretion of IL-4 and IL-5, and this indicates that 9CRA may have anti-inflammatory effects on mast cells.

• Journal of Acupuncture Research
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• 제20권4호
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• pp.85-92
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• 2003

목적 : 허혈시 발생되는 저산소중 상태에서는 세포독성을 유발한다고 알려져 있으나 정확한 기전은 아직 규명되지 않았다. 본 연구에서는 뇌허혈로 인한 세포독성의 기전을 유전자 발현을 통하여 살펴보고자 하였다. 방법 : 본 실험에서는 BV-2 microglia 세포주에 12시간 동안의 저산소 상태에서의 유전자 발현을 분석하기 위하여 마이크로에레이를 시행하였다. 결과 : 저산소 상태에서는 정상에 비하여 cathepsin F, growth factor independent 1, calcitonin/calcitonin-related poly, leucine-rich repeat LGI family membrane, dublecortin, cyclohydrolase 1, Ia-associated invariant chain, carbohydrate kinase-like과 erythrocyte protein band 4.1-like 3 등의 유전자 발현이 3배 이상 증가하였다. 한편 neuronal guanine nucleotide exchange factor, Bcl-2-related ovarian killer protein, chemokine (C-X-C motif) ligand 5, RNA binding motif protein 3, interleukin 2 receptor, alpha chain, crystallin zeta, cytochrome P450 subfamily IV B, asparagine synthetase과 moesin 등의 유전자 발현은 0.2배 이하로 감소하였다. 결론 : 이상의 결과는 저산소중에 관여하는 유전자 및 저산소중과 관련된 뇌경색 등의 질환의 기전을 밝히는데 기초적 자료로 이용될 수 있을 것이다.