• Journal of Periodontal and Implant Science
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• v.29 no.2
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• pp.333-350
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• 1999

The modulation of leukocyte cell surface adhesion molecules may influence the development of cellular events that determine the course of the inflammatory process. Direct interaction between activated T cells and monocytes resulted in a large production of $IL-1{\beta}$ by monocytes. In this reactions, adhesion molecules play an important part, yet the role of them in Tmonocytes interaction remain unclear. This study was undertaken in an effort to elucidate, 1) the influence of 1.25(OH)$_2D_3-induced$ differentiation on the monocyte responsiveness to direct contact with T lymphocytes, and 2) the role of adhesion molecules on the T-monocyte direct interaction. Initially, I observed that direct contact of monocyte cell line THP-1 with stimulated fixed T cell line HuT78 markedly induces IL-1${\beta}$ production by THP-1. $IL-1{\beta}$ production was higher when THP-1 had been previously exposed to 1.25(OH)$_2D_3$ as compared to control, with ${\alpha}$- 1.25(OH)$_2D_3$ dose-dependent and exposure time-dependent manner. It was shown that 1.25(OH)$_2D_3$ also increased the expression of ${\beta}_2$ integrin adhesion receptor Mac-1(CD11b/CD18) dose- and timedependently, but did not increase the expression of human leukocyte antigen- D(HLA-D) and intercellular adhesion molecule-1(ICAM-1). The $IL-1{\beta}$ producing activity of THP-1 cells correlated well with the ability to induce the Mac-1 expression on THP-1 surface. Monoclonal antibody raised against relevant cell surface glycoproteins on THP-1 were tested for their ability to block the response of THP-1 to T cells. Antibody to Mac-1 only partially blocked $IL-1{\beta}$ production by THP-1, whereas antibodies to ICAM-1 and HLA-D did not. These data indicate that regulation of Mac-1 expression on THP-1 cells can alter the responsiveness of these cells to contact by activated T cells, however other unknown structures on the THP-1 cells may be involved in this process also.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.1
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• pp.49-60
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• 2008

Objective: This study was carried out to investigate the effects of 3-dimensional co-culture of human endometrial cells decidualized with progesterone and TGF-${\beta}1$ on the development of 2-cell mouse embryos. Methods: Stromal and epithelial cells isolated from human endometrial tissue were immunostained for cytokeratin and vimentin. Expression of TGF-${\beta}1$, its receptor-1, -2, integrin-${\beta}3$ and prolactin in mono or co-culture according to three different hormone conditions was investigated by RT-PCR. Differential staining was used to investigate the number of ICM and trophectoderm of hatched mouse blastocysts in different three conditions. Results: The immunohistochemical study was positive for cytokeratin or vimentin and confirmed that epithelial and stromal cells were isolated from endometrial tissue successfully. In co-culture, TGF-${\beta}1$, its receptor-1, integrin-${\beta}3$ and prolactin except TGF-${\beta}1$-r2 were expressed in progesterone dominant condition. The hatching and attaching rate were higher in the co-culture with decidualized cells (p<0.05). However, we observed that lots of the incomplete hatched blactocysts attached on non-decidualized cells. The ICM number of hatched mouse blastocysts was higher in co-culture with decidualized and non decidualized cells than media only culture (p<0.05). The trophectoderm number of hatched blastocyst was higher in the co-culture with decidualized cells than non-decidualized cells or media only culture (p<0.05). Conclusion: The administration of progesterone, estrogen and TGF-$\beta$ could induce decidualization of stromal and epithelial cells isolated from human endometrial tissue using 3-dimensional co-culture, and the decidualization of human endometrial cells could increase the hatching and attaching rate of 2-cell mouse embryos.

• Clinical and Experimental Reproductive Medicine
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• v.27 no.2
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• pp.117-131
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• 2000

Objectives: To develop a new immunohistochemical marker system for supplementation of the Noyes histological classification of the endometrium in women of child bearing age with regular menstrual cycles, and to employ this system to evaluate pathologic factors involved in endometriosis, and thus to ascertain if it is useful in diagnosis. Materials and Methods: Endometrial biopsies were sampled from the posterior fundus of 41 (24 proliferative phases, 17 secretory phases) women with regular menstrual cycles (28-32 days), and each sample was immunohistochemically stained according to Noyes et al (1975) for determination of expression for estrogen receptor (ER), progesterone receptor (PR), integrin ${\alpha}_1$, ${\alpha}_4$, ${\beta}_3$, COX-1 and COX-2. Then, the PR, integrin ${\beta}_3$ and COX-2 which were clearly expressed in the luteal phase was with endometrial samples were obtained from 20 cases of normal patients (group 1) and 25 cases with endometriosis (group 2) after confirming the day of ovulation by sex steroid level measurements 7-8 days after ovulation Results: In the regular menstruation group the expression of ER showed a tendency to be increased in the proliferative phase and decreased in the secretory phase, and was the highest in the proliferative phase. However, PR in the stromal cells showed no change in the entire menstrual cycle while in the epithelial cells, PR reached a peak in the late proliferative phase and was almost absent in the secretory phase. Integrin (${\alpha}_1$, ${\alpha}_4$, and ${\beta}_3$ expression in the epithelial cells was absent in the proliferative phase but ${\alpha}_1$ was strongly expressed starting from the early secretory phase into the entire secretory phase. ${\alpha}_4$ was expressed strongly in the early and mid secretory phases and disappeared in the late proliferative phase, while ${\beta}_3$ appeared after the mid secretory phase and continued to be expressed until the late secretory phase. Expression in the stromal cells was weak overall and did not show any cyclic pattern. COX-1 expression was shown as a cyclic pattern in the stromal and epithelial cells and was particularly strongly expressed in the mid secretory phase of epithelial cells, and in the mid secretory and menstruation phase of stromal cells. In the endometrial epithelial cells there was strong expression during the entire cycle with stronger expression in the secretory phase compared to the prolferative phase. COX-2 was clearly expressed in the late proliferative, early and mid secretory phases in the stromal cells. No expression was observed in the proliferative phase of the epithelial cells, but which began to appear in the early secretory phase reaching a significant pattern from the mid secretory phase onwards. There was almost no expression in the stromal cells. In the cases with endometriosis showing normal endometrial maturation according to the Noyes classification, PR expression was increased while Integrin-${\beta}_3$의 expression was significantly decreased compared to the normal group. Also, COX-2 expression was slightly decreased in the stromal cells of patients with endometriosis while it was significantly increased in the stromal cells. Conclusion: Immunohistochemical markers can supplement the original Noyes classification of histological endometrial dating and therefore ascertain existing pathologic conditions. Particularly for patients with endometriosis with normally mature endometrial cells, changes in COX-2 and integrin expression patterns may assist in elucidating pathophysiologic mechanisms and therefore aid in the diagnosis of abnormal implantation conditions, and consequently determine a treatment modality.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.279-285
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• 2015

Background: Korean Red Ginseng has been used as a traditional oriental medicine to treat illness and to promote health for several thousand years in Eastern Asia. It is widely accepted that ginseng saponins, ginsenosides, are the major active ingredients responsible for Korean Red Ginseng's therapeutic activity against many kinds of illness. Although the crude saponin fraction (CSF) displayed antiplatelet activity, the molecular mechanism of its action remains to be elucidated. Methods: The platelet aggregation was induced by collagen, the ligand of integrin ${\alpha}_{II}{\beta}_I$ and glycoprotein VI. The crude saponin's effects on granule secretion [e.g., calcium ion mobilization and adenosine triphosphate (ATP) release] were determined. The activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38 MAPK, and phosphoinositide 3-kinase (PI3K)/Akt was analyzed by immunoblotting. In addition, the activation of integrin ${\alpha}_{II}b{\beta}_{III}$ was examined by fluorocytometry. Results: CSF strongly inhibited collagen-induced platelet aggregation and ATP release in a concentration-dependent manner. It also markedly suppressed $[Ca^{2+}]_i$ mobilization in collagen-stimulated platelets. Immunoblotting assay revealed that CSF significantly suppressed ERK1/2, p38, JNK, PI3K, Akt, and mitogen-activated protein kinase kinase 1/2 phosphorylation. In addition, our fraction strongly inhibited the fibrinogen binding to integrin ${\alpha}_{IIb}{\beta}_3$. Conclusion: Our present data suggest that CSF may have a strong antiplatelet property and it can be considered as a candidate with therapeutic potential for the treatment of cardiovascular disorders involving abnormal platelet function.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.3
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• pp.306-318
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• 2008

Anodic spark deposition method(ASD) surface treated titanium implant possesses a considerable osteoconductive potential that promoting a high level of implant osseointegration in normal bone. The purpose of this study was to observe the ASD implant's osseointegration in the osteoporosis-induced animal model. Twenty four rats, 10 weeks of age, were ovarectomized and 5 weeks later divided into two groups : ASD implant group and control implant group. Titanium screw implants (diameter; 2.0 mm, length, 3.5 mm; pitch-height, 0.4 mm) were designed for this study. Experimental implants were ASD treated and no treatment on control implants. ASD implants and control implants were placed in to left tibiae of rats. The rats were sacrificed at different time interval(1, 2, 4 and 8 weeks after implantation) for histopathologic observation and immunohisto-chemistrical observation, with collagen type Ⅰ, fibronectin, integrin ${\alpha}_2{\beta}_1$ and integrin ${\alpha}_5{\beta}_1$ antibodies. The results obtained from this study were as follow: 1. Histopathologic findings, overall tissue response and the pattern of bone formation in both groups were similar. In ASD group, more newly formed bone was seen at 1 week and 2weeks than control group. 2. The levels of type Ⅰ collagen and fibronectin expression were the most abundant at 2weeks and decreased gradually in both groups. Fibronectin and type Ⅰ collagen expression in ASD group were stronger than control group but no significance. 3. The levels of integrin ${\alpha}_2{\beta}_1$ and Integrin ${\alpha}_5{\beta}_1$ expression were most abundant at 2 weeks and decreased gradually in both groups. No significant difference was observed in both groups. From this results, anodic oxidized titanium implants were more advantages in early stage of bone formation than control group, but have no significance in tissue responses and late bone formations. It could be stated that although anodic oxidized titanium implant possesses considerable osteoconductive potential but in osteoporotic bone condition dental implant procedure should performed after improving or treating the osteoporotic bone condition.

• Korean Journal of Medicinal Crop Science
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• v.15 no.2
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• pp.89-94
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• 2007

The effects of angiogenesis inhibitor from the extract libraries of Korean and Chinese medicinal plants were investigated using a protein microarray chip. Protein chip was constructed by immobilization of integrin ${\alpha}_5{\beta}_1$ on protein chip base plates and employed far screening active extracts that inhibit the integrin-fibronectin interaction from the extract libraries. The 100 extracts of medicinal plants were obtained from extract bank of National Institute of Crop Science, RDA. The 14 extracts among 100 extract libraries were shown efficient inhibition activity for the interaction between integrin-fibronectin. The medicinal plants of 14 extracts were Vitex negundo var. incisa (Lam.) C.B. Clarke, Epimedium koreanum Nakai, Cedrela sinensis A. Juss, Ipomea aquatica Forsk, Schisandra chinensis Baill, Pulsatilla koreana Nakai, Paeonia lactiflora Pall. var.hortensis Makino, Oenothera odorata, Allium chinense, Allium victorialis var. platyphyllum MAKINO, Polygonatum odoratum Druce var. pluriflorum Ohwi, Hosta lancifolia, Agrimonia pilosa L. var. japonica Nakai and Potentilla chinensis SER. The Paeonia lactiflora, Oenothera, and Agrimonia pilosa from these 14 extracts libraries were shown strong inhibition activity of integrin ${\alpha}_5{\beta}_1$.

• Animal cells and systems
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• v.9 no.3
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• pp.161-171
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• 2005

Integrin-linked kinase 1 (ILK1) regulates several protein kinases, including PKB/Akt kinase and glycogen synthase kinase ${\beta}$. ILK1 is also involved distinctively in the cell morphological and structural functions by interacting with the components of the extracellular matrix or integrin. According to the information of serum- and glucocorticoid-induced kinase 1 (SGK1) substrate specificity (R-X-R-X-X(S/T)-${\phi};{\phi}$ indicates a hydrophobic amino acid), two putative phosphorylation sites, $Thr^{181}\;and\;Ser^{246}$, were found in ILK1. We showed that ILK1 fusion protein and two fluorescein-labeled ILK1 peptides, $FITC-^{174}RTRPRNGTLN^{183}$ and $FITC-^{239}CPRLRIFSHP^{248}$, were phosphorylated by SGK1 in vitro. We also identified that 14-3-3 ${\theta}\;{\varepsilon}\;and\;{\xi}$, among several 143-3 isotypes $({\beta},\;{\gamma},\;{\varepsilon},\;{\eta},\;{\sigma},\;{\theta},\;{\tau}\;and\;{\xi})$ formed protein complex with ILK1 in COS-1 cells. Furthermore, the phosphorylation of $Ser^{246}$ by SGK1 induced the binding with 14-3-3. It was also demonstrated that 14-3-3-bound ILK1 has reduced kinase activity. Thus, these data suggest that SGK1 phosphorylates $Thr^{181}\;and\;Ser^{246}$ of ILK1 and the phosphorylation of its $Ser^{246}$ makes ILK1 bind to 14-3-3, resulting in the inhibition of ILK1 kinase activity.

• Journal of Life Science
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• v.21 no.2
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• pp.286-291
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• 2011

Hypoxia is a common condition found in a wide range of solid tumors and is often associated with metastasis and poor clinical outcomes. In the present study, we found that HIF-$1{\alpha}$ was induced by cobalt chloride (500 ${\mu}M$) treatment on human lung cancer cells, A549 and H460, for 24 hr. However, cobalt chloride (500 ${\mu}M$) did not affect cell proliferation of A549 and H460 in 48 hr. Cobalt chloride (500 ${\mu}M$) additionally induced epithelial-to-mesenchymal-like transition (EMT) such as reduced E-cadherin expression and increased ${\alpha}$-SMA expression. These results were confirmed by immunofluorecence experiment in H460 cells. E-cadherin was localized on the outer cell membrane. However, when the cells were treated with 500 ${\mu}M$ cobalt chloride for 24 hr, diffuse E-cadherin staining was observed, characteristic of a migratory mesenchymal phenotype. We also found that cobalt chloride induced integrin ${\beta}3$ expression and FAK phosphorylation in human lung cancer cells using western blotting and FACS anlaysis. Our data suggest that integrin ${\beta}3$-induced FAK phosphorylation may be developed into target molecules for blocking tumor metastasis.

• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.18-24
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• 2019

Andrographolide, the main compound of Andrographis paniculata (A. paniculata), shows various biological properties including anti-viral, anti-inflammatory, anti-diabetic, and hepatoprotective effects. Our previous study has shown that A. paniculata extract exerts antiaging effects by activation of stemness in epidermal stem cells (EpSCs). In this study, we investigated the effect of andrographolide as a main compound of A. paniculata on EpSCs and its mechnism of action using several in vitro assays. Andrographolide increased the proliferation of EpSCs and induced cell cycle progression. Additionally, andrographolide increased VEGF production and the expression of stem cell markers integrin ${\beta}1$ and p63. Furthermore, phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), S6 ribosomal protein (S6RP) and Akt were increased by andrographolide. Taken together, these results indicate that andrographolide-induced proliferation of EpSCs is mediated by the ERK1/2, Akt-dependent pathway with increased production of VEGF and upregulated stemness through integrin ${\beta}1$ and p63.

• Genomics & Informatics
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• v.8 no.1
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• pp.9-18
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• 2010

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (${\beta}1$) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and $P^{corr}=0.05$). The minor allele frequency (MAF) of ITGB1 haplotype -2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.