• International Journal of Oral Biology
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• v.40 no.3
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• pp.127-133
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• 2015

The salivary gland undergoes complex process of growth and differentiation of the branching morphogenesis of ductal system during the prenatal and early postnatal periods which are regulated by various elements in the extracellular matrix. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell adhesion molecule. In the present study, localization and expression of EMMPRIN in development and effects of chorda-lingual denervation and cyclosporine A (CsA) treatment on the EMMPRIN expression were investigated. Immunohistochemistry, RT-PCR and Western blot were used to determine expression level. Immunohistochemistry revealed that EMMPRIN was localized specifically in the cytoplasm of ductal cells, not acini of the submandibular gland all the postnatal periods. At prenatal day 18, when the formation of ducts was not definite, no immunoreactivity was observed. Both Western blot and RT-PCR analyses revealed that EMMPRIN expression was maintained up to postnatal day 7, decreased after postnatal day 10. The EMMPRIN expression was upregulated by the surgical denervation of the chorda-lingual nerve in the gland as well as by the CsA treatment. The present study suggests that EMMPRIN is a crucial molecule for maintaining physiological functions of the salivary gland.

• BMB Reports
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• v.41 no.8
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• pp.593-596
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• 2008

ADPKD (Autosomal Dominant Polycystic Kidney Disease) is characterized by the progressive expansion of multiple cystic lesions in the kidneys. ADPKD is caused by mutations in Ed-pl. consider PKD1 and PKD2. Recently a relation between c-myc and the pathogenesis of ADPKD was reported. In addition, c-Myc is a downstream effector of PKD1. To identify the gene regulated by PKD2 and c-Myc, we performed gene expression profiling in PKD2 and c-Myc overexpressing cells using a human 8K cDNA microarray. NCAM (neuronal cell adhesion molecule) levels were significantly reduced in PKD2 overexpressing systems in vitro and in vivo. These results suggest that NCAM is an important molecule in the cystogenesis induced by PKD2 overexpession.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.635-641
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• 2011

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved with suppressed oxidative stress, cell adhesion molecules, and pro-inflammatory factors. The aim of this study was to determine whether green tea seed coat ethyl acetate fraction (GTSCE) could modulate cell adhesion molecules and inflammatory mediators in HUVEC stimulated with TNF-${\alpha}$. Nitric oxide (NO) production was significantly increased in TNF-${\alpha}$-stimulated HUVEC compared to TNF-${\alpha}$ only treated cells. The NO that is produced by endothelial nitric oxide synthase dilates blood vessels and has protective effects against platelet and leucocyte adhesion. GTSCE at 25, 50, 75, and $100\;{\mu}g$/mL significantly (p<0.05) reduced TNF-${\alpha}$ production. GTSCE significantly (p<0.05) inhibited soluble vascular cell adhesion molecule-1 level, in a dose-dependent manner. Monocyte chemoattractant protein-1 level was also significantly (p<0.05) inhibited by GTSCE treatment at $75\;{\mu}g$/mL compared to the TNF-${\alpha}$-only treated group. Total antioxidant capacity by GTSCE was significantly (p<0.05) enhanced compared to the TNF-${\alpha}$-only treated group. These results suggest that GTSCE can inhibit the production of cell adhesion molecules and inflammatory mediators and could be used as a candidate bioactive material to prevent the development of atherosclerosis.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.377-384
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• 2017

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of $PKC{\beta}II$ on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral $PKC{\beta}II$ gene transfer and pharmacological inhibitors, the role of $PKC{\beta}II$ on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by $PKC{\beta}i$ (10 nM), a selective inhibitor of $PKC{\beta}II$. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by $PKC{\beta}i$. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of $PKC{\beta}II$ inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of $PKC{\beta}II$ using adenoviral $PKC{\beta}II$ increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, $PKC{\beta}II$-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that $PKC{\beta}II$ plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of $PKC{\beta}II$-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.

• Journal of Chest Surgery
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• v.33 no.3
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• pp.213-220
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• 2000

Background: Adhesion of leukocytes to myocardium or vascular endothelium has been known as an importation initial step in the ischemia-reperfusion injury which may affect the cardiac function. Therefore, leukocyte-depleted reperfusion may inhibit ischemia-reperfusion induced functional and ultrastructural deterioration. In this study, we quantified the time-dependent expression of the vascular cell adhesion molecule-1(VCMA-1) on piglet myocardium and demonstrated its relation to functional recovery using isolated piglet heart perfusion model. Material and Method: Neonatal(1 to 3 day old) piglet heart was harvested with 4$^{\circ}C$ University of Wisconsin solution (UWS) and presrved in the same solution for 12 hours. Ex vivo model of an isolated working neonatal piglet heart perfusion consisting of membrane oxygenator and roller-pump was used (Fig. 1). Hearts were grouped into leukocyte-non-depleted (group A, n=8) and leukocyte-depleted group(group B, n=8). In group B, hearts were reperfused with leukocyte-depleted blood using a leukocyte filter (Sepacell R, Asahi Medical, Japan). Segments of right atrium were taken before and after 1, 2, 3, and 4 hours of reperfusion for the evaluation of expression of VCAM-1. The intensity of immunohistochyemical satining of the VCAM-1 on the myocardium were graded semiquantitatively (0 to 4). For the evaluation of myocardial stroke work indices were calculated as well at the same time-points. Result: Mean expressins of VCAM-1 on the myocardium at 0, 1, 2, 3, adn 4 hours of reperfusion were 0.63, 1.44, 1.64, 2.65, and 3.34 in group A, while 0.56, 1.40, 1.50, 1.88 and 2.14 in group B (Fig. 3). Mean stroke work indices at 0.5, 1, 2, 3, and 4 hours after reperfusion were 1.35$\times$104, 1.32$\times$104, 1.14$\times$104, 0.81$\times$104, 0.68$\times$104 erg/gm in group A, while 1.40$\times$104, 1.43$\times$104, 1.43$\times$104, 1.28$\times$104, and 1.12$\times$104 erg/em in group B(Fig. 4). Conclusion : In this study, we demonstrated that leukocyte-depletion attenuated the expression of VCAM-1 during reperfusion and the time-dependent functional deterioration of the myocardium was well correlated with the degree of VCAM-1 expression.

• Journal of Chest Surgery
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• v.35 no.2
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• pp.87-93
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• 2002

Background: Predicting the important role of intercellular adhesion molecule-1 expression on the acute ischemia-reperfusion injury, we set out to demonstrate it by assessing the degree of expression of ICAM-1 after warm ischemia-reperfusion in canine unilateral lung ischemia model. Material and Method: Left unilateral lung ischemia was induced by clamping the left hilum for 100 minutes in seven adult mongrel dogs. After reperfusion, various hemodynamic pararmeters and blood gases were analyzed for 4 hours, while intermittently clamping the right hilum in order to allow observation of the injured Ieft lung function. The pulmonary venous blood was collected serially to measure TNF- and cICAM-1 level. After 4 hours of reperfusion, the lung tissue was biopsied to assess cICAM-1 expression, and to measure tissue malondialdehyde(MDA) and ATP level. Result: The parameters including arterial oxygen partial pressure, pulmonary vascular resistance and tissue MDA and ATP level suggested severe lung damage. Serum TNF-$\alpha$ level was 8.76$\pm$2.37 ng/ml at 60 minutes after reperfusion and decreased thereafter. The cICAM-1 level showed no change after the reperfusion during the experiment. The tissue cICAM-1 expression was confirmed in 5 dogs. Conclusion: The increase of TNF-$\alpha$ Ievel and expression of tissue ICAM-1 were demonstrated after ischemia reperfusion injury in canine lung model.

• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1629-1635
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• 2012

Previously, we demonstrated that the erythropoietin receptor (EpoR) is present on fibroblasts, where it regulates focal contact. Here, we assessed whether this action of EpoR is involved in the reduced cell adhesion observed in colonocytes exposed to Clostridium difficile toxin A. EpoR was present and functionally active in cells of the human colonic epithelial cell line HT29 and epithelial cells of human colon tissues. Toxin A significantly decreased activating phosphorylations of EpoR and its downstream signaling molecules JAK-2 (Janus kinase 2) and STAT5 (signal transducer and activator of transcription 5). In vitro kinase assays confirmed that toxin A inhibited JAK 2 kinase activity. Pharmacological inhibition of JAK2 (with AG490) abrogated activating phosphorylations of EpoR and also decreased focal contacts in association with inactivation of paxillin, an essential focal adhesion molecule. In addition, AG490 treatment significantly decreased expression of occludin (a tight junction molecule) and tight junction levels. Taken together, these data suggest that inhibition of JAK2 by toxin A in colonocytes causes inactivation of EpoR, thereby enhancing the inhibition of focal contact formation and loss of tight junctions known to be associated with the enzymatic activity of toxin A.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.3
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• pp.47-65
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• 2023

Objectives We evaluated the wound healing effects of Dangguijakyak-san (DJ) using C57BL/6 mice that were generated open wound. Methods The study was conducted with seven C57BL/6 mice assigned to each group, divided into the normal group, control group, vitamin E group, DJ low-dose group, DJ high-dose group. We measured total polyphenol, flavonoid contents, the size of the wound, liver function, pro-inflammatory cytokine activity in serum, inflammation-related proteins, adhesion molecules and chemokine proteins, collagen-related proteins in skin tissue and histopathological changes by H&E and Masson's staining. Results DJ treatment significantly reduced the area of the wound compared to the control group. Also, inflammatory cytokines were reduced and the expression of anti-inflammatory-related factors (interleukin-4 [IL-4] and IL-10) was significantly increased in the DJ treatment group. We identified that DJ treatment inhibits both pathways of inflammation, the mitogen-activated protein kinases and nuclear factor-κB pathway. Moreover, the protein expressions of Sirt1 (sirtuin 1), MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), and VCAM-1 (vascular cell adhesion molecule 1) were decreased by DJ administration. Also, the expression of α-smooth muscle actin and collagen type I alpha 1, collagen-related proteins, that help skin recovery was significantly increased in the DJ treatment group. Histopathologically, a relatively thin epithelial layer could be observed in the DJ administration group, as well as an increase in fibroblasts and collagen fibers. Conclusions These data suggest that DJ treatment is effective in wound healing, suppressing inflammatory proteins, increasing skin repair factors and improving histopathological changes caused by wounds.

• Molecules and Cells
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• v.28 no.3
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• pp.183-188
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• 2009

TSAd/Lad is a T cell adaptor molecule involved in $p56^{lck}$-mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the $p56^{lck}$ proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as $Ca^{2+}$ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.

• Korean Journal of Pharmacognosy
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• v.44 no.2
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• pp.131-137
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• 2013

The present study has been undertaken to investigate the effect of the extract of Cirsium japonicum var. ussuriense leaves (CLE) on blood circulation in a rat model of topical ferric chloride ($FeCl_3$)-induced carotid artery damage. $FeCl_3$ treatment seriously damaged the carotid artery such as the walls of the artery, blood flow and inflammation. However, CLE administration has ameliorated blood circulation and suppressed vessel inflammation. CLE administration also has ameliorated the $FeCl_3$-induced artery tissue damage. Furthermore, CLE significantly suppressed the expression of adhesion molecules. These results suggest that CLE ameliorate blood circulation through suppress inflammatory mediator and adhesion molecule production.