• Tuberculosis and Respiratory Diseases
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• 제66권3호
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• pp.205-210
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• 2009

연구배경: CXCR3 리간드인 케모카인 CXCL10과 CXCL11은 세포면역 활성 시 interferon-$\gamma$에 의해 발현이 유도되어, T 림프구와 자연살생세포의 소집 및 활성도를 증가시키고 폐 감염 시 활성화된 기관지 상피 세포에서도 발현된다. 이에 저자들은 세포면역을 활성화 시킬 수 있는 폐암과 결핵감염에서의 CXCL11의 표현을 CXCL10과 함께 정량적으로 비교하여 활동성 결핵감염의 표지자로서 활용 가능성을 알아보고자 하였다. 방법: 2007년 1월부터 12월까지 부산대학교병원 호흡기 내과를 방문한 신규환자 중 폐암과 결핵이 의심되는 환자를 대상으로 전향적 연구를 시행하였다. 환자는 조직학적 그리고 임상적으로 47명의 폐암군, 18명의 활동성 폐결핵군, 그리고 대조군으로 38명의 양성폐질환군으로 분류하였다. 혈청에서 CXCL10과 CXCL11의 농도는 효소면역측정법을 이용하여 측정하였다. 결 과: CXCL10과 CXCL11은 활동성 폐결핵군에서 폐암군과 양성폐질환군에 비해 유의하게 증가되었다(p<0.001, Kruskal-Wallis). CXCL11은 폐암군이 양성 폐질환군에 비해 유의하게 높았으나, CXCL10은 차이가 없었다(각각, p<0.001, p=0.655, Mann-Whitney U). 폐암군에서 CXCL10은 stage III+IV군에서 stage I+II군에 비해 높았지만, CXCL11은 병기에 따른 유의한 차이를 보이지 않았다(p<0.001, p=0.07, Mann-Whitney U). 폐암의 전이 유무에서는 CXCL10과 CXCL11 모두 유의한 차이를 보이지 않았다. CXCL10과 CXCL11간에는 서로 유의한 상관관계가 있었다(r=0.223, p<0.001). 결 론: CXCL10과 CXCL11은 폐암을 포함한 타 폐질환에 비해 활동성 폐결핵에서 유의하게 증가되었다. 따라서, 활동성 폐결핵에 기존의 진단법과 함께 유용한 지표로서 사용될 수 있을 것이다.

• 생명과학회지
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• 제21권5호
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• pp.664-670
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• 2011

Heat shock protein (HSP)은 외부적인 자극에 반응하여 세포를 보호하는 역할을 한다. 또한 HSP90은 혈관질환에서 처럼 세포가 사멸되거나 손상을 입는 경우 세포 밖으로 유리된다. 그러나 지금까지 세포 밖 HSP90이 혈관평활근세포에 어떠한 영향을 주는지에 대한 연구는 미약하다. 따라서 본 연구는 혈관평활근세포에서 HSP90이 CXCL10 발현에 대한 영향과 그 기전을 규명하였다. HSP90에 노출된 혈관평활근세포에서 CXCL10 transcript가 증가하고, CXCL10 단백질의 분비가 증가되었다. HSP90에 의한 CXCL10 분비는 Toll-like receptor (TLR)-2/-4 억제제인 1-palmitoyl-2-arachidonosyl-sn-phosphatidylcholine (OxPAPC)과 NADPH oxidase 억제제인 diphenyleneiodium 그리고 Akt 경로를 억제하는 LY294002와 Akti IV에 의하여 크게 감소되었다. 또한 TLR-4의 dimerization을 저해하는 curcumin 역시 HSP90에 의한 CXCL10의 분비를 억제하였다. 전사인자인 nuclear factor kappa B(NF-${\kappa}$B)의 생물학적 억제제인 inhibitory kappa B (I${\kappa}$B)와 NF-${\kappa}$B 억제작용이 있는 rasveratrol은 HSP90에 의한 CXCL10 분비를 억제하였다. 이러한 결과는 혈관평활근세포에서 HSP90에 의한 CXCL10의 발현에 TLR-4와 Akt 및 NF-${\kappa}$B가 관여함을 의미한다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5403-5408
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• 2013

Objective: CXCL12 exerts a wide variety of chemotactic effects on cells. Evidence indicates that CXCL12, in conjunction with its receptor, CXCR4, promotes invasion and metastasis of tumor cells. Our objective was to explore whether the CXCL12-CXCR4 biological axis might influence biological behavior of pancreatic cancer cells. Methods: Miapaca-2 human pancreatic cancer cells were cultured under three different conditions: normal medium (control), medium + recombinant CXCL12 (CXCL12 group), or medium + CXCR4-inhibitor AMD3100 (AMD3100 group). RT-PCR was applied to detect mRNA expression levels of CXCL12, CXCR4, matrix metalloproteinase 2 (MMP-2), MMP-9, and human urokinase plasminogen activator (uPA). Additionally, cell proliferation and invasion were performed using CCK-8 colorimetry and transwell invasion assays, respectively. Results: CXCL12 was not expressed in Miapaca-2 cells, but CXCR4 was detected, indicating that these cells are capable of receiving signals from CXCL12. Expression of extracellular matrix-degrading enzymes MMP-2, MMP-9, and uPA was upregulated in cells exposed to exogenous CXCL12 (P<0.05). Additionally, both proliferation and invasion of pancreatic cancer cells were enhanced in the presence of exogenous CXCL12, but AMD3100 intervention effectively inhibited these processes (P<0.05). Conclusions: The CXCL12-CXCR4 biological axis plays an important role in promoting proliferation and invasion of pancreatic cancer cells.

• IMMUNE NETWORK
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• 제9권3호
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• pp.106-113
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• 2009

Background: We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. Methods: Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 ($AT_1$) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [$^3H$]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. Results: Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the $AT_1$ receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an $AT_1$ receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. Conclusion: These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.

• Genomics & Informatics
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• 제20권3호
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• pp.31.1-31.15
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• 2022

A pandemic of respiratory disease named coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is reported prostate cancer patients are susceptible to COVID-19 infection. To understand the possible causes of prostate cancer patients' increased vulnerability and mortality from COVID-19 infection, we focused on the two most important agents, transmembrane protease serine subtype 2 (TMPRSS2) and the C-X-C motif 10 (CXCL10). When SARS-CoV-2 binds to the host cell via S protein-angiotensin-converting enzyme-2 receptor interaction, TMPRSS2 contributes in the proteolytic cleavage of the S protein, allowing the viral and cellular membranes to fuse. CXCL10 is a cytokine found in elevated level in both COVID-19 and cancer-causing cytokine storm. We discovered that TMPRSS2 and CXCL10 are overexpressed in prostate cancer and COVID-19 using the UALCAN and GEPIA2 datasets. The functional importance of TMPRSS2 and CXCL10 in prostate cancer development was then determined by analyzing the frequency of genetic changes in their amino acid sequences using the cBioPortal online portal. Finally, we used the PANTHER database to examine the pathology of the targeted genes. We observed that TMPRSS2 and CXCL10, together with their often co-expressed genes, are important in the binding activity and immune responses in prostate cancer and COVID-19 infection, respectively. Finally, we found that TMPRSS2 and CXCL10 are two putative biomarkers responsible for the increased vulnerability and fatality of prostate cancer patients to COVID-19.

• IMMUNE NETWORK
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• 제16권3호
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• pp.189-194
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• 2016

Obesity is characterized as an accumulation of adipose tissue mass represented by chronic, low-grade inflammation. Obesity-derived inflammation involves chemokines as important regulators contributing to the pathophysiology of obesity-related diseases such as cardiovascular disease, diabetes and some cancers. The obesity-driven chemokine network is poorly understood. Here, we identified the profiles of chemokine signature between human preadipocytes and adipocytes, using PCR arrays and qRT-PCR. Both preadipocytes and adipocytes showed absent or low levels in chemokine receptors in spite of some changes. On the other hand, the chemokine levels of CCL2, CCL7-8, CCL11, CXCL1-3, CXCL6 and CXCL10-11 were dominantly expressed in preadipocytes compared to adipocytes. Interestingly, CXCL14 was the most dominant chemokine expressed in adipocytes compared to preadipocytes. Moreover, there is significantly higher protein level of CXCL14 in conditioned media from adipocytes. In addition, we analyzed the data of the chemokine signatures in adipocytes obtained from healthy lean and obese postmenopausal women based on Gene Expression Omnibus (GEO) dataset. Adipocytes from obese individuals had significantly higher levels in chemokine signature as follows: CCL2, CCL13, CCL18-19, CCL23, CCL26, CXCL1, CXCL3 and CXCL14, as compared to those from lean ones. Also, among the chemokine networks, CXCL14 appeared to be the highest levels in adipocytes from both lean and obese women. Taken together, these results identify CXCL14 as an important chemokine induced during adipogenesis, requiring further research elucidating its potential therapeutic benefits in obesity.

• Journal of Yeungnam Medical Science
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• 제24권1호
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• pp.67-78
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• 2007

Interferon-${\gamma}$ (IFN-${\gamma}$)의 주된 생산세포는 림프구이며 주로 Interleukin-18(IL-18)에 의해 생산이 된다. IP-10은 IFN-${\gamma}$에 의해 유도, 생산되는 대표적인 케모카인이다. 따라서 본 연구는 마우스 복강내 대식세포에서의 IL-18에 의한 IP-10의 생산 여부를 관찰하고자하였다. IL-18은 마우스 복강내 대식세포에서 IP-10의 발현을 직접적으로 유도 하지는 않았다. 그러나 대식세포에 지다당질을 처리하기 전 IL-18을 전 처리 시킨 결과 지다당질에 의해 유도된 IP-10의 발현이 항진되어 나타남을 확인하였다. 이러한 항진 효과는 IL-18 전처리 16시간에 나타났으며, 이때 NF-${\kappa}B$의 활성이 IP-10의 발현 항진과 일치함을 확인하였다. 비록 IL-18이 IP-10을 직접적으로 발현시키지는 못하나 NF-${\kappa}B$의 활성을 통하여 IL-18의 적정시간에 따른 전 처리시 IP-10 발현의 항진은 케모카인 발현에있어 IL-18의 작용기전을 이해하는데 유용한 자료가 될 것이다.

• 대한의생명과학회지
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• 제28권3호
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• pp.200-205
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• 2022

Established cancer cell lines are widely used for developing biomarkers for the patient-specific treatment of colorectal cancer and predicting prognoses. However, cancer cell lines may exhibit different drug responses depending upon the characteristics of the cell line. Therefore, it is necessary to select a tumor cell line suitable for the purpose of the study by considering the cell characteristics. This study investigated the levels of CXCL10, which were recently been reported to play an important role in the outcome of tumor treatment, secreted by colon cancer cells. 2 × 10⁵ cells/mL of each colorectal cancer cell was seeded into a 35 mm cell culture dish. After 24 h incubation, culture supernatant was used to determine the secreted CXCL10 levels. Among six colorectal cancer cell lines (HT-29, HCT116, CaCo-2, SW620, SW480, and CT26), Caco-2 cells showed the highest level of CXCL10 secretion. HT-29 cells showed the second-highest level of CXCL10 secretion. No significantly measurable level of CXCL10 secretion was detected in HCT116 cells. These results will be helpful in investigating the molecular basis of colorectal cancer.

• Molecules and Cells
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• 제22권2호
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• pp.163-167
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• 2006

Histone deacetylase (HDAC) activity is commonly associated with transcriptional repression. However, there is also evidence for a function in transcriptional activation. Previous studies have demonstrated a fundamental role of deacetylase activity in $IFN{\alpha}$-responsive gene transcription. In the case of type II IFN ($IFN{\gamma}$) results are controversial: some genes require HDAC activity, while transcription of others is repressed by HDAC. To investigate the effect of HDAC on transcription of an $IFN{\gamma}$-activated gene, real-time PCR was used to measure CXCL10 mRNA in Hela cells stimulated with $IFN{\gamma}$ in the presence or absence of the HDAC inhibitor TSA. Chromatin imunoprecipitation combined with real-time PCR was used to check acetylation of histone H4 and recruitment of the STAT1 complex to the ISRE locus of the CXCL10 gene. Activation of CXCL10 transcription in response to $IFN{\gamma}$ was paralleled by a decrease in histone H4 acetylation and an increase in recruitment of the STAT1 complex to the CXCL10 ISRE locus. The transcription of CXCL10 and histone H4 deacetylation were blocked by TSA, but the latter had no obvious affect on recruitment of the STAT1 complex. Our data indicate that $IFN{\gamma}$ and STAT-dependent gene transcription requires the participation of HDAC, as does the $IFN{\alpha}$-STAT pathway.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.564-570
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• 2015

Peptidoglycan (PG), the gram positive bacterial pathogen-associated molecular patterns (PAMP), is detected in a high proportion in macrophage-rich atheromatous regions, and expression of chemokine CXCL8, which triggers monocyte arrest on early atherosclerotic endothelium, is elevated in monocytes/ macrophages in human atherosclerotic lesion. The aim of this study was to investigate whether PG induced CXCL8 expression in the cell type and to determine cellular signaling pathways involved in that process. Exposure of THP-1 cell, human monocyte/macrophage cell line, to PG not only enhanced CXCL8 release but also profoundly induced il8 gene transcription. PG-induced release of CXCL8 and induction of il8 gene transcription were blocked by OxPAPC, an inhibitor of TLR-2/4 and TLR4, but not by polymyxin B, an inhibitor of LPS. PG-mediated CXCL8 release was significantly attenuated by inhibitors of PI3K-Akt-mTOR pathways. PKC inhibitors, MAPK inhibitors, and ROS quenchers also significantly attenuated expression of CXCL8. The present study proposes that PG contributes to inflammatory reaction and progression of atherosclerosis by inducing CXCL8 expression in monocytes/macrophages, and that TLR-2, PI3K-Akt-mTOR, PKC, ROS, and MAPK are actively involved in the process.