Biomedical subjects

Inpyo Choi

Publications and source records attributed to Inpyo Choi.

18 recordsLinked to original sources

PubMed2006

Adiponectin is a negative regulator of NK cell cytotoxicity.

NK cells are a key component of innate immune systems, and their activity is regulated by cytokines and hormones. Adiponectin, which is secreted from white adipose tissues, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. In this study the effect of adiponectin on NK cell activity was investigated. Adiponectin was found to suppress the IL-2-enhanced cytotoxic activity of NK cells without affecting basal NK cell cytotoxicity and to inhibit IL-2-induced NF-kappaB activation via activation of the AMP-activated protein kinase, indicating that it suppresses IL-2-enhanced NK cell cytotoxicity through the AMP-activated protein kinase-mediated inhibition of NF-kappaB activation. IFN-gamma enhances NK cell cytotoxicity by causing an increase in the levels of expression of TRAIL and Fas ligand. The production of IFN-gamma, one of the NF-kappaB target genes in NK cells, was also found to be suppressed by adiponectin, accompanied by the subsequent down-regulation of IFN-gamma-inducible TRAIL and Fas ligand expression. These results clearly demonstrate that adiponectin is a potent negative regulator of IL-2-induced NK cell activation and thus may act as an in vivo regulator of anti-inflammatory functions.

Adiponectin↗

PubMed2006

Soluble ULBP suppresses natural killer cell activity via down-regulating NKG2D expression.

NKG2D is an activating receptor that is expressed on most natural killer (NK) cells and CD8(+) T cells. MHC class I-related chain A(MICA) and UL16-binding protein (ULBP) 1, 2, and 3 are well-known ligands for NKG2D. Human gastric cancer cell lines, SNU216 and SNU638 cells which expressed UL16-binding protein (ULBP) were susceptible to NK cells in a NKG2D-dependent manner. However, SNU484 and SNU620 cells which had no ULBP on their surface were resistant to NK cells. ULBP 1, 2, and 3 are glycosylphosphatidylinositol (GPI)-anchored proteins which are sensitive to phosphatidylinositol-specific phospholipase C (PI-PLC). When SNU620 cells were treated with U73122, an inhibitor of PI-PLC, the surface expression of ULBP was elevated with increased NK susceptibility. Pre-incubating NK cells with culture supernatants of SNU620 or SNU638 cells, which contained soluble ULBP protein, reduced NK cell activity by decreasing surface expression of NKG2D in NK cells. Furthermore, recombinant ULBP-Fc induced the down-regulation of NKG2D expression in NK cells. Taken together, down-regulation of NKG2D by soluble ULBP provides a potential mechanism by which gastric cancer cells escape NKG2D-mediated attack by the immune cells.

Carrier Proteins↗

PubMed2006

Vitamin D3 upregulated protein 1 (VDUP1) is a regulator for redox signaling and stress-mediated diseases.

Vitamin D(3) upregulated protein 1 (VDUP1) is a 46-kDa multifunctional protein, initially isolated in HL-60 cells as a protein of which expression is upregulated by vitamin D(3) administration. Subsequently, it was identified independently by investigators from diverse scientific backgrounds as a thioredoxin binding protein that negatively regulates the expression and the activity of thioredoxin, and is thus involved in redox regulation. Further studies have revealed that VDUP1 plays multiple roles in a wide range of cellular processes such as proliferation or apoptosis. Recently, it has been reported that VDUP1 is also involved in the immune system via positive regulation of natural killer development. In addition, VDUP1 has been revealed to be associated with the fatty acid utilization. In the present review, we discuss the novel aspects of VDUP1 function as well as the historical background of VDUP1. Future studies will explore the diagnostic and therapeutic potential of modulating the function of VDUP1 in vivo.

Carrier Proteins↗

PubMed2005

Apolipoprotein A-I induces IL-10 and PGE2 production in human monocytes and inhibits dendritic cell differentiation and maturation.

Apolipoprotein A-I (apoA-I), the major protein component of serum high-density lipoprotein, exhibits anti-inflammatory activity in atherosclerosis. In this study, we demonstrate that apoA-I inhibits DC differentiation and maturation. DC differentiated from monocytes in the presence of apoA-I showed a decreased expression of surface molecules such as CD1a, CD80, CD86, and HLA-DR. In addition, these DC exhibited decreased endocytic activity and weakened allogeneic T-cell activation. During DC differentiation in the presence of apoA-I, PGE(2) and IL-10, which are known to be DC differentiation inhibitors and/or modulators of DC function, were produced at remarkable rates, whereas IL-12 production in the cells after stimulation with CD40 mAb and IFN-gamma was significantly decreased in comparison with the control DC. T cells stimulated by apoA-I-pretreated DC produced significantly low levels of IFN-gamma, and apoA-I inhibited cross-talk between DC and NK cells, in terms of IL-12 and IFN-gamma production. Therefore, apoA-I appears to play an important role in modulating both innate immune response and inflammatory response. The novel inhibitory function of apoA-I on DC differentiation and function may facilitate the development of new therapeutic interventions in inflammatory diseases.

Apolipoprotein A-I↗

PubMed2005

Stage-dependent gene expression profiles during natural killer cell development.

Natural killer (NK) cells develop from hematopoietic stem cells (HSCs) in the bone marrow. To understand the molecular regulation of NK cell development, serial analysis of gene expression (SAGE) was applied to HSCs, NK precursor (pNK) cells, and mature NK cells (mNK) cultured without or with OP9 stromal cells. From 170,464 total individual tags from four SAGE libraries, 35,385 unique genes were identified. A set of genes was expressed in a stage-specific manner: 15 genes in HSCs, 30 genes in pNK cells, and 27 genes in mNK cells. Among them, lipoprotein lipase induced NK cell maturation and cytotoxic activity. Identification of genome-wide profiles of gene expression in different stages of NK cell development affords us a fundamental basis for defining the molecular network during NK cell development.

Animals↗

PubMed2005

Tumor suppressor VDUP1 increases p27(kip1) stability by inhibiting JAB1.

Vitamin D3 up-regulated protein 1 (VDUP1) is a stress-response gene that is up-regulated by 1,25(OH)2D3 in many cells. It has been reported that VDUP1 expression is reduced in many tumor cells and the enforced expression of VDUP1 inhibits cell proliferation by arresting cell cycle progression. Here, we found that VDUP1-/- fibroblast cells proliferated more rapidly compared with wild-type cells with reduced expression of p27(kip1), a cyclin-dependent kinase inhibitor. JAB1 is known to interact with p27(kip1) and to decrease the stability of p27(kip1). VDUP1 interacted with JAB1 and restored JAB1-induced suppression of p27(kip1) stability. In this process, VDUP1 blocked the JAB1-mediated translocation of p27(kip1) from the nucleus to the cytoplasm. In addition, VDUP1 inhibited JAB1-mediated activator protein-1 activation and cell proliferation. Taken together, these results indicate that VDUP1 is a novel factor of p27(kip1) stability via regulating JAB1.

Animals↗

PubMed2005

The interferon-inducible 9-27 gene modulates the susceptibility to natural killer cells and the invasiveness of gastric cancer cells.

As an effort to identify immune suppressive molecules in gastric cancer cells, a signal sequence trap was employed. Among the genes identified, 9-27 gene was highly expressed in gastric tumor tissues and in cancer cell lines. It was induced by IFN-gamma treatment, but not by TNF-alpha or TGF-beta1 treatment. The overexpression of 9-27 in the gastric cancer cells rendered tumor cells more resistant to natural killer cells. In addition, the 9-27-overexpressed cells showed an increased migration and an invasive capacity when compared with the control cells. Taken together, these data indicate that 9-27 plays a role in malignant progression by suppressing natural killer cells and by increasing the invasive potential of gastric cancer cells.

Adenocarcinoma↗

PubMed2005

c-Jun N-terminal kinase is involved in the suppression of adiponectin expression by TNF-alpha in 3T3-L1 adipocytes.

Adiponectin, one of adipokines that is secreted from adipocytes, plays an important role in the regulation of glucose and lipid metabolism. Paradoxically, serum concentrations of adiponectin are decreased in obese and type 2 diabetic patients, although it is produced in adipose tissue. On the other hand, plasma TNF-alpha levels are increased in such subjects. In the present study, the mechanism by which adiponectin is regulated by TNF-alpha was investigated. The decreased adiponectin mRNA levels by TNF-alpha were partially recovered by treatment with a c-Jun N-terminal kinase (JNK) inhibitor or the PPAR-gamma agonist rosiglitazone in 3T3-L1 adipocytes. Interestingly, however, cotreatment with the JNK inhibitor and rosiglitazone led to a recovery of TNF-alpha-mediated adiponectin suppression to the control level. The JNK inhibitor regulated the expression of adiponectin by the increase of PPAR-gamma DNA binding activity and the recovery of its mRNA expression while rosiglitazone acted via a PPAR-gamma independent pathway which remains to be elucidated. These findings suggest that the JNK signaling pathway, activated by TNF-alpha, is involved in the regulation of adiponectin expression.

3T3-L1 Cells↗

PubMed2005

VDUP1 is required for the development of natural killer cells.

Vitamin D3 upregulated protein 1 (VDUP1) is a stress-response gene that is upregulated by 1,25(OH)2D3 in tumor cells. The in vivo roles of VDUP1 were investigated by producing mice lacking VDUP1 (VDUP1-/- mice). VDUP1-/- mice showed minimal changes in the development of T and B cells, but there was a profound reduction in the numbers of natural killer (NK) cells. As well, these mice showed decreased NK activity. In the VDUP1-/- mice, the expression of CD122 was reduced, demonstrating that VDUP1 is required for CD122 expression and NK maturation. In addition, severe lymphoid hyperplasia in the small intestine was observed in VDUP1-/- mice. Taken together, these results suggest that VDUP1 is a critical factor for the development and function of NK cells in vivo.

Animals↗

PubMed2005

Silanimonas lenta gen. nov., sp. nov., a slightly thermophilic and alkaliphilic gammaproteobacterium isolated from a hot spring.

A moderately thermophilic aerobic bacterium, strain 25-4T, was isolated from a hot spring at Baekdoo Mountain in Korea. The cells were Gram-negative, motile rods each having a polar flagellum. Analysis of the 16S rRNA gene sequence indicated that the strain represented a new lineage within the family 'Xanthomonadaceae' of the 'Gammaproteobacteria', being most closely related to the genera Thermomonas, Xanthomonas, Luteimonas, Pseudoxanthomonas, Stenotrophomonas and Xylella and having 16S rRNA gene sequence similarities to the most related species of the genera of between 92.9 and 94.4 %. The strain contained Q-8 as the major isoprenoid quinone and had a fatty acid profile with predominant iso-branched fatty acids. Growth occurred at pH 6.0-10, with an optimum at pH 9.0, and at 25-53 degrees C, with an optimum at 47 degrees C. The G+C content of the genomic DNA was 50.7 mol%. On the basis of phylogenetic analyses and its phenotypic characteristics, strain 25-4T belongs to a new genus, Silanimonas gen. nov., within the 'Gammaproteobacteria'. The sole species of this genus is Silanimonas lenta sp. nov. (type strain, 25-4T=DSM 16282T=KCTC 12236T).

Bacterial Typing Techniques↗

PubMed2004

Heat shock factor regulates VDUP1 gene expression.

The vitamin D3 up-regulated protein 1 (VDUP1) is identified as interacting protein with thioredoxin (TRX) and functions as a natural antagonist of TRX. Its expression is regulated by various stresses including ROS, UV, and heat shock. In the present study, we observed an inducible expression of VDUP1 in Bosc cells by high density and serum deprivation cultures. To determine transcription factors associated with the induction of VDUP1 by stresses, the promoter region of VDUP1 was cloned. Through reporter assays with plasmids having various deletion of its promoter region and analysis of putative cis-elements, heat shock factor element (HSE) was identified. The deletion of HSE abolished transcriptional activity of VDUP1 promoter by stresses and the binding of heat shock factor (HSF) to HSE was confirmed by gel-shift and supershift assays using nuclear extracts prepared from stressed Bosc cells. Also, the enforced expression of HSF or heat shock increased the transcription of endogenous VDUP1. These imply that HSF is an important transcription factor involved in up-regulation of VDUP1 expression by stresses such as high density and serum deprivation cultures.

Base Sequence↗

PubMed2003

Macrophage inhibitory cytokine-1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system.

In our search for genes associated with gastric cancer progression, we identified macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor beta superfamily, as an overexpressed gene in gastric tumor tissues. Expression analysis of MIC-1 in gastric tumor tissues revealed a specific expression in gastric cancer cells, and this expression level was well correlated with invasive potential in various human gastric cancer cell lines. Stable transfection of MIC-1 into SNU-216, a human gastric cancer cell line, significantly increased its invasiveness. The overexpression of MIC-1 into SNU-216 cells significantly increased the activity of urokinase-type plasminogen activator (uPA), and the expressions of uPA and urokinase-type plasminogen activator receptor (uPAR). Similarly, the stimulation of gastric cancer cell lines with purified recombinant MIC-1 dose-dependently increased cell invasiveness, uPA activity, and uPA and uPAR expression. However, MIC-1 did not significantly suppress the proliferation of gastric cancer cell lines. We also found that the stimulation of human gastric cell lines with recombinant MIC-1 strongly induced activation of mitogen-activated protein kinase kinase-1/2 and extracellular signal-regulated kinase-1/2. Additional analysis revealed that PD98059, a selective inhibitor of mitogen-activated protein kinase kinase-1/2, suppressed not only gastric cancer cell invasiveness and uPA activity, but also the mRNA expressions of uPA and uPAR, as induced by recombinant MIC-1. Our results indicate that MIC-1 may contribute to the malignant progression of gastric cancer cells by inducing tumor cell invasion through the up-regulation of the uPA activation system via extracellular signal-regulated kinase-1/2-dependent pathway.

Cell Division↗

PubMed2003

Aberrant signaling of TGF-beta1 by the mutant Smad4 in gastric cancer cells.

TGF-beta1 has been known to suppress the growth of gastric cancer cells. Interestingly, TGF-beta1 treatment increased the proliferation of human gastric cancer cell line, SNU-216 cells, while it reduced the proliferation of other tumor cells including SNU-620 cells. TGF-beta1-mediated down-regulation of c-Myc and induction of p21CIP1 were observed in SNU-620, but there was no change in SNU-216 in response to TGF-beta1. Similarly, TGF-beta1 receptors were upregulated by TGF-beta1 treatment in SNU-620, but they were not responded in SNU-216. By a single strand conformation polymorphism analysis, a repeated insertion of 37 nucleotides in the exon 8 of Smad4, resulting in premature termination at codon 362, was found in SNU-216. Furthermore, this truncated Smad4 functioned as a dominant negative form in TGF-beta1-mediated reporter activity and TGF-beta1 receptor expression. However, the proliferation of tumor cells was not affected by Smad4 mutation, but it was modulated by PD98059. Taken together, a mutation in Smad4 in addition to mitogen-activated protein kinase altered the TGF-beta1-mediated signaling, which is one of key events of gastric tumorigenesis.

DNA-Binding Proteins↗

PubMed2003

VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression.

Vitamin D(3) upregulated protein 1 (VDUP1) is a 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) upregulated protein, and it is induced by various stresses. In human tumor tissues, VDUP1 expression was downregulated. Upon stimulation by growth-inhibitory signals such as TGF-beta1 and 1,25(OH)(2)D(3), its expression was rapidly upregulated as the cell growth was retarded. The transfection of VDUP1 in tumor cells reduced cell growth. The VDUP1 expression was also increased when the cell-cycle progression was arrested. Transfection of VDUP1 induced cell-cycle arrest at the G0/G1 phase, indicating that VDUP1 possesses a tumor-suppressive activity. In addition, it was found that VDUP1 interacted with promyelocytic leukemia zinc-finger, Fanconi anemia zinc-finger, and histone deacetylase 1, which are known to be transcriptional corepressors. VDUP1 itself suppressed IL-3 receptor and cyclin A2 promoter activity. Taken together, these results suggest that VDUP1 is a novel antitumor gene which forms a transcriptional repressor complex.

3T3 Cells↗

PubMed2003

Dexamethasone reverses TGF-beta-mediated inhibition of primary rat preadipocyte differentiation.

Dexamethasone and transforming growth factor-beta (TGF-beta) show contrary effects on differentiation of adipocytes. Dexamethasone stimulates adipocyte differentiation whereas TGF-beta inhibits it. In the present study, we investigated whether dexamethasone could reverse the TGF-beta-mediated inhibition of preadipocyte differentiation. Primary rat preadipocytes, obtained from Sprague-Dawley rats, were pretreated with dexamethasone in the presence or absence of TGF-beta, prior to the induction of differentiation. Co-treatment of dexamethasone and TGF-beta before inducing differentiation reversed the TGF-beta-mediated inhibition of preadipocyte differentiation. In order to elucidate the mechanism by which dexamethasone reversed the effect of TGF-beta on the inhibition of preadipocyte differentiation, the expression of CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) was examined. Dexamethasone increased C/EBPalpha and PPARgamma expression in the absence of TGF-beta and also recovered the TGF-beta-mediated suppression of C/EBPalpha expression in preadipocytes. Its effect was sustained in differentiated adipocytes as well. However, those effects were not observed in 3T3-L1 preadipocytes or differentiated adipocytes. These results indicate that dexamethasone reverses the TGF-beta-mediated suppression of adipocyte differentiation by regulating the expression of C/EBPalpha and PPARgamma, which is dependent on the cellular context.

Adipocytes↗

PubMed2003

Vitamin D(3) up-regulating protein 1 (VDUP1) antisense DNA regulates tumorigenicity and melanogenesis of murine melanoma cells via regulating the expression of fas ligand and reactive oxygen species.

The expression of vitamin D(3) up-regulating protein-1 (VDUP1) was up-regulated by 1alpha,25-dihydroxyvitamin D(3) (VD3) treatment in B16 mouse melanoma cells. The functional effect of VDUP1 on B16F10 melanoma cells was demonstrated by reduction of Fas ligand and CD44 expression in cells transfected with VDUP1 antisense cDNA. Furthermore, intracellular reactive oxygen species level and cell proliferation were decreased in antisense transfectants compared with those in vector controls. However, melanin synthesis was up-regulated in antisense transfectants. In addition, VDUP1 antisense transfectants showed an increased susceptibility to natural killer (NK) cells in vitro. When VDUP1 antisense transfectants were implanted into syngeneic mice, significant reduction of tumor cell growth was observed with the infiltrate of T cells and NK cells in tumor area. Taken together, these results demonstrate that VDUP1 has critical physiological roles and can be a novel therapeutic target for melanoma.

Animals↗

PubMed2002

Interleukin-12 p40 gene expression is induced in lipopolysaccharide-activated pituitary glands in vivo.

Proinflammatory cytokines have several functions including activation of the hypothalamo-pituitary-adrenal (HPA) axis and regulation of the immune system. The present study focuses on the regulation of interleukin 12 (IL-12) and its receptor gene expression in the HPA axis under artificially induced immune stress, brought on by administration of lipopolysaccharide (LPS) to Sprague-Dawley (SD) rats. RT-PCR analyses showed that expression of the IL-12 p40 gene was significantly increased and peaked at 2 h in the pituitary gland, but not in the hypothalamus. LPS-induced IL-12 p40 gene induction in the pituitary gland was suppressed after beta-adrenoceptor agonist pretreatment in vivo. Both IL-12 p40 gene induction and IL-12 production were also observed when freshly isolated pituitary glands from non-treated SD rats were incubated with LPS in vitro. Furthermore, CD14, which is known as a LPS receptor, was found to be expressed in the pituitary gland. Gel mobility shift assays using nuclear extracts prepared from the pituitary glands of rats administered LPS showed induction of NF-kappaB and AP-1 DNA-binding activity. These results suggest that LPS stimulates the pituitary gland directly in vivo to increase IL-12 p40 gene expression and IL-12 protein production.

Animals↗

PubMed2002

Plasma cell granuloma in cyclosporine-induced gingival overgrowth: a report of two cases with immunohistochemical positivity of interleukin-6 and phospholipase C-gamma1.

We report two cases of gingival plasma cell granuloma in a 34-yr-old and 40-yr-old two male renal transplant recipients with cyclosporine A (CsA)-induced gingival overgrowth (GO). Histologically, these lesions were composed of mature plasma cells, showing polyclonality for both lambda and kappa light chains and fibrovascular connective tissue stroma. In addition to the fact that CsA-induced plasma cell granuloma is rare, the salient features of our cases were the secretion of interleukin-6 and overexpression of phospholipase C- gamma 1 of the tumor cells, which may explain the mechanisms of CsA- induced GO.

Cyclosporine↗