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Min Kyung Jung,
Youn Kyung Houh,
Soogyeong Ha,
Yoolhee Yang,
Daejin Kim,
Tae Sung Kim,
Suk Ran Yoon,
Sa Ik Bang, Byung Joo Cho,
Wang Jae Lee,
Hyunjeong Park,
Daeho Cho
[show abstract]
[hide abstract]
ABSTRACT: Erythroid differentiation regulator 1 (Erdr1) suppressed cell motility in vitro and has anti-metastatic effect in vivo on melanoma. The current study investigated the effect of recombinant Erdr1 on the migration and invasion ability of SNU-216 cell, a gastric cancer cell line. The expression of Erdr1 is inversely correlated with IL-18 expression, which has a pro-cancer effect in gastric cancer. Treatment with rErdr1 markedly suppressed the ability of SNU-216 cells to migrate and invade, indicating that recombinant Erdr1 inhibited the motility of gastric cancer cells. E-cadherin expression levels were measured to determine the factor involved in the rErdr1-suppressed motility. E-cadherin is a representative of the cadherin family, known as cell motility enhancement adhesion molecule. Our results revealed that E-cadherin levels were increased by rErdr1 treatment, suggesting the involvement of E-cadherin in rErdr1-reduced cell migration. The cells were treated with specific MAPK inhibitors such as SP600125, SB203580 or PD98059 to identify the signaling mechanism involved with rErdr1 suppressed cell migration. The results indicated that the rErdr1 inhibited migration was primarily reversed by SP600125, a JNK inhibitor. In addition, the level of JNK phosphorylation was markedly increased by recombinant Erdr1. Taken together, these findings suggest that rErdr1 suppressed the ability of gastric cancer cells to metastasis by up regulating E-cadherin through a JNK pathway activation. Furthermore, it can be suggested that the inhibitory effect of recombinant Erdr1 on SNU-216 cell's metastatic potential was through cell motility suppression.
Immunology letters 01/2013; · 2.91 Impact Factor
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Kyoung Tak Ma,
Chan Yun Kim,
Gong Je Seong,
Seung Hyuck Lee,
Jong Woon Park,
Seung Joo Ha, Byung Joo Cho,
Jeanette A Stewart,
Michael S Kristoffersen,
Lindsay A Nelson,
William C Stewart
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the potential benefit of intraocular pressure (IOP) reduction in normal-tension glaucoma (NTG) patients in South Korea. A retrospective, multi-center analysis of Korean NTG patients with 5-years follow-up, typical glaucomatous optic disc and/or visual field changes and no recorded IOP >21 mmHg. Progression was identified by Advanced Glaucoma Intervention Study visual field scoring. There were 90 (42%) progressed patients and 127 (58%) stable patients included in the study. Mean IOP measured higher in the progressed (14.3 ± 2.2 mmHg) than stable patients (14.0 ± 1.9 mmHg), but was not statistically different between the groups (P = 0.29). The mean IOP that best discriminated stable patients was ≤15 mmHg, but no statistical difference existed in the numbers of progressed versus stable patients at ≤15 mmHg compared to >15 mmHg (P = 0.07). Multivariate regression analysis showed that the baseline number of glaucoma medicines and visual field as well as mean, peak and fluctuation of IOP were significant risk factors for glaucomatous progression (P < 0.01). This study suggests that in Korean NTG patients, despite relatively similar IOPs between progressed and stable patients, and based on multivariate regression analysis, IOP may be a risk factor for glaucomatous progression.
International Ophthalmology 09/2011; 31(5):355-61.
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Min Kyung Jung,
Yoorim Park,
Seok Bean Song,
So Young Cheon,
Sunyoung Park,
Younkyung Houh,
Soogyeong Ha,
Hee Jung Kim,
Jung Min Park,
Tae Sung Kim,
Wang Jae Lee, Byung Joo Cho,
Sa Ik Bang,
Hyunjeong Park,
Daeho Cho
[show abstract]
[hide abstract]
ABSTRACT: Erythroid differentiation regulator (Erdr1) was first discovered in mouse leukemia cell lines and functions as a stress-related survival factor. This study investigated whether Erdr1 regulates murine melanoma progression, as well as the mechanism involved in Erdr1-regulated metastasis. The expression of Erdr1 is negatively correlated with IL-18 expression, which has a pro-cancer effect in melanoma. To study the role of Erdr1 as an anti-cancer factor, cell migration, invasion, and proliferation were measured. Erdr1 overexpression markedly inhibited the level of cell migration, invasion, and proliferation in B16F10 cells in vitro. In addition, Erdr1 overexpression significantly suppressed melanoma lung colonization, metastasis, and tumor growth in vivo. To identify the factors involved in Erdr1-reduced metastasis, heat shock protein 90 (HSP90), a well-known stress protein and contributor to tumor metastasis, was examined. We found that HSP90 was significantly decreased in Erdr1-overexpressing cells. Functional analysis demonstrated that HSP90 small-interfering RNA transfection reduced the migration ability and metastasis of melanoma. In conclusion, Erdr1 shows a powerful anti-metastasis effect that leads to the ability to reduce the metastatic potential of murine malignant melanoma cells. Erdr1 is an anti-metastatic factor that may be a possible therapeutic target for treatment of melanoma.
Journal of Investigative Dermatology 06/2011; 131(10):2096-104. · 6.31 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To compare the peripapillary retinal nerve fiber layer (RNFL) thickness of normal patients and those with various glaucoma diseases by time domain (Stratus) and spectral domain (Spectralis) optical coherence tomography (OCT).
The RNFL thickness as measured by the Stratus and Spectral OCT was compared (paired t-test). The relationship and agreement of RNFL thickness between the two OCT modalities were evaluated by Pearson correlation, Bland-Altman plot, and area under the receiver operating characteristic curve.
Two-hundred seventeen eyes of 217 patients, including twenty-four normal eyes, ninety-one glaucoma suspects, seventy-six normal tension glaucoma cases, and twenty-six primary open angle glaucoma cases (POAG) were analyzed. The peripapillary RNFL thicknesses as measured by Stratus OCT were significantly greater than those measured by Spectralis OCT. However, in quadrant comparisons, the temporal RNFL thickness obtained using Stratus OCT were significantly less than those obtained using Spectralis OCT. Correlations between RNFL parameters were strong (Pearson correlation coefficient for mean RNFL thickness = 0.88); a high degree of correlation was found in the POAG group. Bland-Altman plotting demonstrated that agreement in the temporal quadrant was greater than any other quadrant.
Both OCT systems were highly correlated and demonstrated strong agreement. However, absolute measurements of peripapillary RNFL thickness differed between Stratus OCT and Spectralis OCT. Thus, measurements with these instruments should not be considered interchangeable. The temporal quadrant was the only sector where RNFL thickness as measured by Spectralis OCT was greater than by Stratus OCT; this demonstrated greater agreement than other sectors.
Korean Journal of Ophthalmology 06/2011; 25(3):166-73.
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Soyoung Cheon,
Ji Hyung Lee,
Sunyoung Park,
Sa Ik Bang,
Wang Jae Lee,
Do-Young Yoon,
Sung-Soo Yoon,
Taesung Kim,
Hyeyoung Min, Byung Joo Cho,
Hyong Joo Lee,
Ki Woong Lee,
Seung Hwan Jeong,
Hyunjeong Park,
Daeho Cho
[show abstract]
[hide abstract]
ABSTRACT: IL-32 was recently identified as a proinflammatory cytokine that is induced by IL-18 in natural killer (NK) cells and is highly
correlated with inflammatory disorders. However, the relationship between IL-32 and tumor progression is still unknown. In
this study, we investigated whether overexpression of IL-32 affects susceptibility of chronic myeloid leukemia (CML) cells
to NK cells. Interestingly, IL-32α-overexpressing CML cell lines, K562, Kcl22, and BV173, showed higher NK cell-mediated killing.
Flow cytometry analysis revealed that overexpression of IL-32α induced increased expression of Fas and UL16-binding protein
2 (ULBP2) in CML cells. The direct relationship between overexpression of surface molecules by IL-32α and increased NK cell-mediated
killing was confirmed by Fas or ULBP2 siRNA transfection. IL-32α-induced Fas and ULBP2 expression are regulated p38 MAPK.
In addition, the transcription factor Ets1 plays a key role in ULBP2 specific expression by IL-32α overexpression in ULBP
family members. Taken together, these data show that IL-32α stimulates Fas and ULBP2 expression via activation of p38 MAPK,
which increases NK susceptibility of CML cells. Enhanced NK cell susceptibility of CML cells by IL-32α overexpression may
improve the efficiency of NK cell-based immunotherapy.
Journal of Biological Chemistry 04/2011; 286(14):12049-12055. · 4.77 Impact Factor
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Ha Na Kim,
Hyemin Kim,
Joo Myung Kong,
Seyeon Bae,
Yong Sung Kim,
Naeun Lee, Byung Joo Cho,
Seung Koo Lee,
Hang-Rae Kim,
Young-il Hwang,
Jae Seung Kang,
Wang Jae Lee
[show abstract]
[hide abstract]
ABSTRACT: It is known that vitamin C induces apoptosis in several kinds of tumor cells, but its effect on the regulation of the angiogenic process of tumors is not completely studied. Vascular endothelial growth factor (VEGF) is the most well-known angiogenic factor, and it has a potent function as a stimulator of endothelial survival, migration, as well as vascular permeability. Therefore, we have investigated whether vitamin C can regulate the angiogenic process through the modulation of VEGF production from B16F10 melanoma cells. VEGF mRNA expression and VEGF production at protein levels were suppressed by vitamin C. In addition, we found that vitamin C suppressed the expression of cyclooxygenase (COX)-2 and that decreased VEGF production by vitamin C was also restored by the administration of prostaglandin E2 which is a product of COX-2. These results suggest that vitamin C suppresses VEGF expression via the regulation of COX-2 expression. Mitogen-activated protein kinases are generally known as key mediators in the signaling pathway for VEGF production. In the presence of vitamin C, the activation of p42/44 MAPK was completely inhibited. Taken together, our data suggest that vitamin C can down-regulate VEGF production via the modulation of COX-2 expression and that p42/44 MAPK acts as an important signaling mediator in this process.
Journal of Cellular Biochemistry 03/2011; 112(3):894-901. · 2.87 Impact Factor
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Soyoung Cheon,
Ji Hyung Lee,
Sunyoung Park,
Sa Ik Bang,
Wang Jae Lee,
Do-Young Yoon,
Sung-Soo Yoon,
Taesung Kim,
Hyeyoung Min, Byung Joo Cho,
Hyong Joo Lee,
Ki Woong Lee,
Seung Hawn Jeong,
Hyungjeong Park,
Daeho Cho
[show abstract]
[hide abstract]
ABSTRACT: Interleukin-32 (IL-32) was recently identified as a pro-inflammatory cytokine that is induced by IL-18 in natural killer (NK)
cells and is highly correlated with inflammatory disorders. However, the relationship between IL-32 and tumor progression
is still unknown. In this study, we investigated whether overexpression of IL-32α affects susceptibility of chronic myeloid
leukemia (CML) cells to NK cells. Interestingly, IL-32α-overexpressing CML cell lines, K562, Kcl22 and BV173, showed higher
NK cell-mediated killing. Flow cytometry analysis revealed that overexpression of IL-32α induced increased expression of Fas
and UL16-binding protein 2 (ULBP2) in CML cells. The direct relationship between overexpression of surface molecules by IL-32α
and increased NK cell-mediated killing was confirmed by Fas or ULBP2 siRNA transfection. IL-32α-induced Fas and ULBP2 expression
are regulated p38 mitogen-activated protein kinase (p38 MAPK). In addition, the transcription factor Ets1 plays a key role
in ULBP2 specific expression by IL-32α overexpression in ULBP family members. Taken together, these data show that IL-32α
stimulates Fas and ULBP2 expression via activation of p38 MAPK, which increases NK susceptibility of CML cells. Enhanced NK
cell susceptibility of CML cells by IL-32α overexpression may improve the efficiency of NK cell-based immunotherapy.
Journal of Biological Chemistry 02/2011; · 4.77 Impact Factor
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Soyoung Cheon,
Ji Hyung Lee,
Sunyoung Park,
Sa Ik Bang,
Wang Jae Lee,
Do-Young Yoon,
Sung-Soo Yoon,
Taesung Kim,
Hyeyoung Min, Byung Joo Cho,
Hyong Joo Lee,
Ki Woong Lee,
Seung Hwan Jeong,
Hyunjeong Park,
Daeho Cho
[show abstract]
[hide abstract]
ABSTRACT: IL-32 was recently identified as a proinflammatory cytokine that is induced by IL-18 in natural killer (NK) cells and is highly correlated with inflammatory disorders. However, the relationship between IL-32 and tumor progression is still unknown. In this study, we investigated whether overexpression of IL-32 affects susceptibility of chronic myeloid leukemia (CML) cells to NK cells. Interestingly, IL-32α-overexpressing CML cell lines, K562, Kcl22, and BV173, showed higher NK cell-mediated killing. Flow cytometry analysis revealed that overexpression of IL-32α induced increased expression of Fas and UL16-binding protein 2 (ULBP2) in CML cells. The direct relationship between overexpression of surface molecules by IL-32α and increased NK cell-mediated killing was confirmed by Fas or ULBP2 siRNA transfection. IL-32α-induced Fas and ULBP2 expression are regulated p38 MAPK. In addition, the transcription factor Ets1 plays a key role in ULBP2 specific expression by IL-32α overexpression in ULBP family members. Taken together, these data show that IL-32α stimulates Fas and ULBP2 expression via activation of p38 MAPK, which increases NK susceptibility of CML cells. Enhanced NK cell susceptibility of CML cells by IL-32α overexpression may improve the efficiency of NK cell-based immunotherapy.
Journal of Biological Chemistry 02/2011; 286(14):12049-55. · 4.77 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To evaluate the long-term effect of latanoprost on central corneal thickness (CCT) in patients with normal tension glaucoma (NTG).
This was a retrospective study and included 166 eyes of 166 patients [128 with NTG and 38 with glaucoma suspect, suspicious discs with normal visual fields, and an intraocular pressure (IOP) ≤21 mmHg as the control group]. Patients with newly diagnosed NTG and who had not had previous topical glaucomatous treatment were followed ≥24 months and received latanoprost 0.005% monotherapy once a day. CCT measurements were performed with an ultrasound pachymeter. CCT measurements before treatment and 24 months after treatment were analyzed.
There were no significant differences between the latanoprost group and the control group with respect to sex, age, baseline IOP, and CCT. A statistically significant reduction in the mean CCT was observed in the latanoprost group [535.5 ± 37.9 vs. 530.1 ± 36.4 μm (n = 128), P < 0.01], but not in the control group [543.1 ± 40.2 vs. 542.6 ± 37.0 μm (n = 38), P = 0.786].
Long-term use of latanoprost may decrease the CCT in patients with NTG. Therefore, clinicians must be aware of longitudinal CCT variations that may arise throughout the follow-up period for proper IOP targeting and management.
Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2011; 27(1):73-6. · 1.46 Impact Factor
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Sun Young Yoon,
Ha Reum Lee,
Yoorim Park,
Joo Heon Kim,
Soo Young Kim,
Suk Ran Yoon,
Wang Jae Lee, Byung Joo Cho,
Hyeyoung Min,
Jung-Wook Bang,
Hyunjeong Park,
Sa Ik Bang,
Daeho Cho
[show abstract]
[hide abstract]
ABSTRACT: Intratumoral hypoxia has been correlated with distant metastatic potential. Two hypoxia inducible factors (HIFs), HIF-1α and HIF-2α, are induced by hypoxia, and high expression of these proteins has been correlated to angiogenesis and distant metastasis. Thymosin β4 (Tβ4) is frequently highly expressed in cancer, and this overexpression correlates with malignant progression. The objective of this study was to investigate the clinical correlation of HIF-α with Tβ4 and the intracellular functional roles of Tβ4 on HIF-α activation. We examined HIF-1α, HIF-2α and Tβ4 expressions in clinical human breast carcinoma (n=70) by immunohistochemistry. We show that high expression of HIF-1α and HIF-2α strongly correlates with Tβ4 expression (P≤0.0001) and overexpression of Tβ4 correlates significantly with patients with lymph node metastasis (P<0.05) of human breast cancer. Additionally, we demonstrate that hypoxia up-regulates intracellular Tβ4 protein, which then affects HIF-α activity, which is the key in regulating VEGF expression. We confirmed that hypoxia-induced intracellular Tβ4 and HIF-α activities were reduced by interference of Tβ4 expression using Tβ4 shRNA lentivirus. Vascular epidermal growth factor (VEGF)-A, a well-recognized lymphangiogenic cytokine, was also down-regulated, but VEGF-C and VEGF-D expressions were not affected. These findings suggest that the overexpression of Tβ4 is strongly associated with HIF-1α and HIF-2α expression and is also clinicopathologically involved with lymph node metastatic potential of breast cancer through the modulation of HIF-αactivation and induction of VEGF-A. Ultimately, these results highlight Tβ4 as a potentially therapeutic target in malignant cancers.
Oncology Reports 01/2011; 25(1):23-31. · 1.84 Impact Factor
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Naeun Lee,
Seyeon Bae,
Hyemin Kim,
Joo Myung Kong,
Hang-Rae Kim, Byung Joo Cho,
Sung Joon Kim,
Seung Hyeok Seok,
Young-Il Hwang,
Sooin Kim,
Jae Seung Kang,
Wang Jae Lee
[show abstract]
[hide abstract]
ABSTRACT: Alloferon, an immunomodulatory peptide, has antiviral capability against herpesvirus. In this research, we aimed to investigate the effect of alloferon on the regulation of the life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV), and its mechanisms. We also assessed the antiviral activity of alloferon on natural killer (NK) cells as an early antiviral immune responder.
We first examined the change in cell proliferation and the expression of the viral genes in a KSHV-infected cell line, body-cavity-based B lymphoma (BCBL)-1, under the lytic cycle by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment. To elucidate the antiviral mechanism of alloferon, we tested calcium influx and the activation of the extracellular signal-regulated kinase (ERK) pathway. Furthermore, we evaluated the cytotoxicity of NK cells against BCBL-1 by alloferon.
Alloferon effectively recovered the suppressed proliferation of BCBL-1 by TPA, which was achieved by the down-regulation of lytic-cycle-related viral genes, RTA, K8 and vIRF2. To clarify the signal transduction pathways related to the regulation of the viral genes by alloferon, we confirmed that the calcium influx into BCBL-1 was apparently inhibited by alloferon, which preceded the suppression of the phosphorylation of ERK and the activation of AP-1 by TPA. Moreover, when NK cells were exposed to alloferon, their cytolytic activity was improved, and this was mediated by the enhancement of perforin/granzyme secretion.
The results of this study suggest that alloferon can be used as an effective antiviral agent for the regulation of the KSHV life cycle by the down-regulation of AP-1 activity and for the the enhancement of antiviral immunity by up-regulation of NK cell cytotoxicity.
Antiviral therapy 01/2011; 16(1):17-26. · 3.16 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The forkhead transcription factor, Foxp3, is thought to act as a master regulator that controls (suppresses) expression of the breast cancer oncogenes, SKP2 and HER-2/ErbB2. However, the mechanisms that regulate Foxp3 expression and thereby modulate tumor development remain largely unexplored. Here, we demonstrate that Foxp3 up-regulation requires p53 function, showing that Foxp3 expression is directly regulated by p53 upon DNA damage responses in human breast and colon carcinoma cells. Treatment with the genotoxic agents, doxorubicin or etoposide, induced Foxp3 expression in p53-positive carcinoma cells, but not in cells lacking p53 function. Furthermore, knock down of endogenous wild-type p53 using RNA interference abrogated Foxp3 induction by genotoxic agents, and exogenous expression of p53 in cells lacking p53 restored the responsiveness of Foxp3 to DNA-damaging stresses. In addition, Foxp3 knock down blunted the p53-mediated growth inhibitory response to DNA-damaging agents. These results suggest that induction of Foxp3 in the context of tumor suppression is regulated in a p53-dependent manner and implicate Foxp3 as a key determinant of cell fate in p53-dependent DNA damage responses.
Journal of Biological Chemistry 03/2010; 285(11):7995-8002. · 4.77 Impact Factor
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Jae Seung Kang,
Seyeon Y Bae,
Hangrae R Kim,
Yeong Seok Kim,
Daejin J Kim, Byung Joo Cho,
Han-Kwang Yang,
Young-Il Hwang,
Kyungjae J Kim,
Hong Suk Park,
Doukho H Hwang,
Daeho J Cho,
Wang Jae Lee
[show abstract]
[hide abstract]
ABSTRACT: Cancer cells metastasize to the other site after escaping from the immune system and CD70, CD44 and vascular endothelial growth factor (VEGF) play important roles in this process. It is recently reported that interleukin (IL)-18 is closely related with the pathogenesis of skin tumor. Therefore, we investigated the role of endogenous IL-18 from stomach cancer on the immune escape mechanism and metastasis via the regulation of CD70, CD44 and VEGF expression. IL-18 and IL-18R expressions were not only investigated on tumor tissues (n = 10), and sera (n = 20) from stomach cancer patients, but also on human stomach cancer cell lines. IL-18 and IL-18R expressions were found on stomach cancer cell lines and tumor tissues. In addition, IL-18 levels were elevated in sera from cancer patients (P < 0.05), compared with sera from normal individuals. Changes in CD70, CD44 and VEGF expression by flow cytometry, immunoblotting and enzyme-linked immunosorbent assay and immune susceptibility by (51)Cr-release assay were investigated, after silencing or neutralization of endogenous IL-18. CD70 expression was increased and it increases immune susceptibility of cancer cells. In contrast, CD44 and VEGF expression was decreased and it suppresses neovascularization and the metastasis of stomach cancer. After inoculation of IL-18 small interfering RNA (siRNA)-transfected stomach cancer cells into Balb/C (nu/nu) mice, regression of tumor mass was determined by measuring of tumor size. And the number and location of metastatic lesions were investigated by hematoxylin and eosin staining. The regression of tumor mass and the suppression of metastasis were observed in the mice, which are injected with IL-18 siRNA-transfected cell lines. Our data suggest that endogenous IL-18 might facilitate stomach cancer cell immune escape by suppressing CD70 and increasing metastatic ability by upregulating CD44 and VEGF.
Carcinogenesis 07/2009; 30(12):1987-96. · 5.70 Impact Factor
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Ha-reum Lee,
Sun Young Yoon,
Ho-Bum Kang,
Sunyoung Park,
Kyung-Eun Kim,
Young Hoon Cho,
Seonghan Kim,
Chul-woo Kim, Byung Joo Cho,
Wang Jae Lee,
Sa Ik Bang,
Hyunjeong Park,
Daeho Cho
[show abstract]
[hide abstract]
ABSTRACT: Thymosin beta 4 (T beta 4), which is the major G-actin sequestering protein, has been shown to have ubiquitous distribution and multiple biological activities. However, T beta 4's functions in relation to natural killer(NK) cells are still unknown. In this study, we show that synthetic T beta 4 peptide increases NK cell cytotoxicity mediated by intercellular adhesion molecule-1 (ICAM-1) through the secretion of cytolytic granules to target cells. This suggests that T beta 4 is a key activator of NK cell cytotoxicity.
Immunology letters 04/2009; 123(1):72-6. · 2.91 Impact Factor
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Hyunkeun Song,
Kyung-Eun Kim,
Daeyoung Hur,
Jong-Seok Lim,
Young Yang, Byung Joo Cho,
Cherl-Hyun Kim,
Taesung Kim,
Saic Bang,
Wang Jae Lee,
Hyunjeong Park,
Daeho Cho
[show abstract]
[hide abstract]
ABSTRACT: Expression of UL16-binding proteins (ULBPs) has been reported in various cancers, such as leukemia and melanoma, and also in some other cancer cell lines. However, the factors that modulate the expression of ULBPs are not well defined. In this study, we investigated the effects of IL-18 on the expression of NKG2D ligands in leukemia cells. IL-18 treatment increased ULBP2 expression in leukemia cells at the mRNA and protein levels. In addition, PD98059 (an ERK1/2 MAPK inhibitor) and SP600125 (a JNK inhibitor) attenuated IL-18-induced ULBP2 expression in a dose-dependent manner. We observed that ERK1/2 and JNK MAPK phosphorylation increased upon treatment with IL-18. IL-18 elevated CD107a expression in cancer cells and increased the cytotoxic activity of NK cells; therefore, we propose that IL-18 increases the susceptibility of target cells by inducing surface expression of ULBP2. Taken together, these findings suggest that IL-18 may play a critical role in regulating ULBP2 expression via the ERK1/2 and JNK MAPK pathways in leukemia cells.
Immunology Letters 10/2008; 120(1-2):103-7. · 2.53 Impact Factor
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Seung Koo Lee,
Jae Seung Kang,
Da Jung Jung,
Dae Young Hur,
Jee Eun Kim,
Eunsil Hahm,
Seyeon Bae,
Hyung Woo Kim,
Daejin Kim, Byung Joo Cho,
Daeho Cho,
Dong Hoon Shin,
Young-Il Hwang,
Wang Jae Lee
[show abstract]
[hide abstract]
ABSTRACT: Vitamin C plays a crucial role in the suppression of proliferation of several types of cancer. Over-expression of cyclooxygenase (COX)-2 and type I insulin-like growth factor (IGF) receptor are important for proliferation and protection from apoptosis in malignancies. However, its specific mechanisms, especially the interaction between COX-2 expression and IGF-I axis mediated by vitamin C, remain yet to be clarified. Therefore, we investigated the effects of vitamin C on the proliferation of melanoma cells via the modulation of COX-2 expression and IGF-I axis. As a result, we found that 1.0 mM vitamin C inhibits the proliferation of SK-MEL-2 without induction of apoptosis. At that moment, IGF-II production was decreased, followed by the inhibition of COX-2 activity. IGF-IR expression was also down-regulated by vitamin C treatment. It coincided with the result from the inhibition of COX-2 by NS-398 and COX-2 siRNA. In addition, the decreased IGF-IR expression by vitamin C was restored by the treatment of recombinant prostaglandin E2. Finally, we determined whether the signal pathway would be involved in vitamin C-induced IGF-II and IGF-IR down-regulation. When the cells were exposed to SB203580, a specific inhibitor of p38 MAPK, COX-2 expression was dramatically recovered. In addition, phosphorylated p38 MAPK was increased after vitamin C treatment. Taken together, vitamin C suppresses proliferation of the human melanoma cell line SK-MEL2 via the down-regulation of IGF-II production and IGF-IR expression, which is followed by the activation of p38 MAPK and the inhibition of COX-2 expression.
Journal of Cellular Physiology 08/2008; 216(1):180-8. · 3.87 Impact Factor
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ABSTRACT: To determine the normal reference range of pulsatile ocular blood flow (POBF) values in healthy Korean subjects and to find out the factors that may affect them.
A total of 280 eyes of 280 normal subjects were included in this study. Best corrected visual acuity (BCVA), intraocular pressure (IOP), axial length, POBF, systemic blood pressure, and pulse rate were measured. The mean, standard deviation, range, and the 5th and 95th percentiles of POBF were calculated, and the influences of various parameters to POBF were determined by multiple regression analyses.
The mean POBF value was 766.0+/-221.6 microl/min in men and 1021.1+/-249.5 microl/min in women. The 5th and 95th percentiles for POBF values were 486.0 microl/min and 1140.0 microl/min in men and 672.0 microl/min and 1458.0 microl/min in women. The POBF values were significantly influenced by gender, mean blood pressure, pulse rate, and axial length.
Even though the POBF values were influenced by gender, BP, and axial length, we could define the normal reference range of POBF in healthy Koreans.
Korean Journal of Ophthalmology 04/2008; 22(1):6-9.
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Jae Seung Kang,
Sung Joon Kim,
Seyeon Bae,
Joo Myung Kong,
Na-Eun Lee,
Hyung Gun Maeng,
Yong Sung Kim,
Hang-Rae Kim,
Hyemin Kim,
Yong-Jin Kim,
Seung-Pyo Lee,
Kyung-Hee Kim,
Daehee Kim,
Dae-Won Sohn, Byung Joo Cho,
Young-Il Hwang,
Wang Jae Lee
[show abstract]
[hide abstract]
ABSTRACT: Vitamin C scavenges toxic free radicals as an antioxidant, and oxidative stress is considered as a major contributor inducing damage to cardiomyocytes in heart diseases. Also, it is well-known that stress provokes oxidative stress and induces cardiac sudden death. Here we show the effects of vitamin C on the prevention of cardiac damage by stress in gulo(-/-) mice which cannot synthesize vitamin C. Vitamin C-insufficient gulo(-/-) mice under stress showed prominent cardiac damage and expired within 2 weeks. It was accompanied with structural changes in the heart, cardiac dysfunction and severe emphysema. These changes were caused by the elevation of pro-inflammatory cytokines, especially TNF-α, the activation of MMP-2/MMP-9, an increase in oxidative stress and a remarkable decrease in noradrenaline production. Thus, vitamin C insufficiency causes extensive cardiac damage under stress through regulating cytokine and hormone production as well as redox homeostasis, which results in stress-induced sudden death.
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