• International Journal of Oral Biology
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• v.35 no.1
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• pp.27-33
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• 2010

Periodontal disease is a major oral disorder and comprises a group of infections that lead to inflammation of the gingiva and the destruction of periodontal tissues. $PPAR{\gamma}$ plays an important role in the regulation of several metabolic pathways and has recently been implicated in inflammatory response pathways. However, its effects on periodontal inflammation have yet to be clarified. In our current study, we evaluated the anti-inflammatory effects of $PPAR{\gamma}$ on periodontal disease. Human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) showed high levels of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Moreover, these cells also showed upregulated activities for extracellular signal regulated kinase (ERK1/2), inducible nitric oxide synthase (iNOS) and cyclooxygnase-2. However, cells treated with Ad/$PPAR{\gamma}$ and rosiglitazone in same culture system showed reduced ICAM-1, VCAM-1, MMP-2, -9 and COX-2. Finally, the anti-inflammatory effects of $PPAR{\gamma}$ appear to be mediated via the suppression of the ERK1/2 pathway and consequent inhibition of NF-kB translocation. Our present findings thus suggest that $PPAR{\gamma}$ indeed has a pivotal role in gingival inflammation and may be a putative molecular target for future therapeutic strategies to control chronic periodontal disease.

• Journal of Periodontal and Implant Science
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• v.29 no.4
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• pp.803-823
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• 1999

In order to reveal immunopathogenesis of periodontal tissue destruction, it is important to clarify the molecular mechanism of trafficking and retention of activated leukocytes, including monocytes/macrophages. Gingival fibroblasts may be involved in the regulation of inflammatory cell accumulation in the extravascular periodontal connective tissues via cytokine production and surface expression of adhesion molecules. In this study, it was investigated the molecular basis for the adhesive interactions between monocytes and fibroblasts such as peri-odontal ligament fibroblast(PDLF), human gingival fibroblast(HGF), and human dermal fibroblast(HDF). First, it was examined the evidence whether monocyte-fibroblast cell contact may cause signal transduction in fibroblasts. Being directly in contact with fixed human monocyte cell line THP-1, or U937, upregulation of IL-6 production, $TNF-{\alpha}$ mRNA expression and increased cell proliferation could be seen for fibroblasts. IL-6 production induced by monocyte- fibroblast coculture were further increased when fibroblasts had been pretreated with $IFN-{\gamma}$ or $IL-1{\beta}$ , and monocytes with LPS. Next, it was examined the expression of ICAM-1 which has been known to be involved in accumulation and activation of leukocytes in inflammatory diseases such as periodontitis. ICAM-1 was upregulated up to 10-fold on PDLF, HGF, and HDF by exposure to $IFN-{\gamma}$ or $IL-1{\beta}$. Furthermore, anti-ICAM-1 monoclonal antibody clearly blocked cocultureinduced IL-6 production by fibroblasts, suggesting that $ICAM-1/{\beta}_2$integrin pathway is involved in periodontal fibroblastmonocyte interaction. Overall, these findings provide evidence that periodontal fibroblasts could be involved in the accumulation and retention of monocytes/macrophages in periodontal inflammatory lesion at least in part by ICAM-1 expression. In addition, periodontal fibroblast-monocyte interaction could cause activation signals in fibroblasts intracellularly which result in cytokine production and cell proliferation. Thus, periodontal fibroblasts are speculated to play an important role in immunoregulation and tissue destruction in chronic periodontal diseases by interaction with monocytes/macrophages.

• IMMUNE NETWORK
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• v.21 no.2
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• pp.13.1-13.19
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• 2021

Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam, is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of Itgam knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrow-derived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.2
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• pp.208-215
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• 2015

The aim of the study was to investigate the antioxidant activities of ethanol extract of perilla seed (PSE) and its inhibitory effects against major characteristics of cancer cells, such as unrestricted growth and activated metastasis in vitro. The total polyphenol and flavonoid levels of PSE were 222.6 mg gallic acid equivalent/100 g and 285.7 mg quercetin equivalent/100 g, respectively. The radical scavenging activity and ferric reducing antioxidant power of PSE at concentration of 87.5 to $350{\mu}g/mL$ were 24~45% and 28~62%, respectively. Treatment of HCT116 colorectal carcinoma cells and H1299 non-small cell lung carcinoma cells with PSE dose-dependently inhibited growth by 18~94% (at concentration range of 87.5 to $350{\mu}g/mL$) and completely abolished colony formation (at concentration of $175{\mu}g/mL$). PSE was also effective in inhibiting migration of H1299 cells (by 30~37% at concentration range of 87.5 to $350{\mu}g/mL$) and adhesion of both HCT116 and H1299 cells (by 14~16% at concentration of $350{\mu}g/mL$). These results indicate that PSE exerts antioxidant and anti-cancer activities in vitro. It needs to be determined whether or not similar effects can be reproduced in vivo.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.757-765
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• 2000

Background : Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count as a measure of tumor angiogenesis, has been significantly correlated with invasive and metastatic patterns in breast. prostate and cutaneous carcinomas. Materials and Methods : Fifty patients with curatively resected non-small cell lung cancer were evaluated. Tumor tissues embedded in paraffin block were stained by anti CD 31 (PECAM, platelet endothelial cellular adhesion molecule) using immunohistochemical method to assess microvessel count. Microvessels were counted in the most active areas of neovascularization(microscopy, 200$\times$). Results: 1) Mean microvessel count was 47.1$\pm$17.7(per 200$\times$field) in total 50 cases. 2) Mean microvessel count of adenocarcinoma (54.4$\pm$19.9) was significantly higher than that of squamous cancer (43.9$\pm$16.2) (p<0.05), but there were no relationship between microvessel count and TNM stages. 3) Median survival time, 2-year and 5-year survival rates of the low microvascular group (microvessel count<45, 22 cases) were 61 months, 80% and 40%, respectively, and those of the high microvascular group(microvessel count$\geq$45, 28 cases) were 46 months, 75% and 12%, respectively. As results, prognosis of low microvascular group is statistically significantly superior to that of the high microvascular group (p=0.0162, Kaplan-Meier, log-rank). Conclusion : Angiogenesis assessed by microvessel count can be used as one of the significant prognostic factors in non-small cell lung cancer.

• The Korean Journal of Food And Nutrition
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• v.29 no.6
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• pp.998-1007
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• 2016

The objective of this study was to investigate the effects of a lettuce (Lactuca sativa L.) extract on the inflammation of human umbilical vein endothelial cell (HUVEC) and blood lipid improvement in hypercholesterolemic mice fed a high cholesterol diet. The lettuce extract (100% ethanol extract) inhibited the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in HUVEC treated with tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). The lettuce extract suppressed the adhesion of THP-1 to TNF-${\alpha}$-treated HUVEC. The lettuce extract decreased the TNF-${\alpha}$-stimulated production of proinflammatory cytokine interleukin-6, interleukin-8 and chemokine monocyte chemotactic protein 1. In hypercholesterolemic mice, the lettuce extract reduced serum total cholesterol, triglyceride, and low-density lipoprotein-cholesterol level, while the lettuce extract elevated high-density lipoprotein-cholesterol level, resulting in the decrease of atherogenic index and cardiac risk factor level. These results suggested that lettuce extract can be an useful resource to show an anti-inflammatory effect and improve lipid metabolism.

• Animal cells and systems
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• v.1 no.1
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• pp.157-164
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• 1997

Ly-6E.1 antigen was proposed as a regulatory molecule of T lymphocyte activation, a hematopoietic stem cell marker, a memory cell marker, and an adhesion molecule. Though there were several reports suggesting the presence of Ly-6 ligand, the characterization of the ligand was not yet performed, As an attempt to screen the expression of Ly-6E.1 ligand, we prepared a probe for detecting Ly-6E.1 ligand by producing a fusion protein between Ly-6E.1 and $hlgC_{r1}$, A mammalian cell expression vector with Ly-6E.$1/hlgC_{r1}$ chimeric cDNA was transfected in SP2/0-Ag14 myeloma cells, and stable transfectants were selected. The fusion protein was produced as a dimer and maintained the epitopes for monoclonal antibodies specific for Ly-6E.1 and for anti-human lgG antibody. The purified fusion protein through Gammabind G column was used for FACS analyses for the expression of Ly-6E.1 ligand. The fusion protein interacted with several cell lines originating from B cells, T cells, or monocytes. The fusion Protein also strongly stained bone marrow, lymph node, and spleen cells, but thymic cells weakly, if any. The staining was more obvious in C57BL/6 $(Ly-6^b)$ than Balb/c $(Ly-6^a)$ mice. These results suggest that the interaction of Ly-6E.1 with Ly-6E.1 ligand may function both in the stem cell environment and in the activation of mature lymphocytes. The fusion protein may be a valuable tool in characterization of biochemical properties of the Ly-6E.1 ligand and, further, in isolating its cDNA.

• Journal of Acupuncture Research
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• v.25 no.1
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• pp.25-55
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• 2008

Objectives : The aim of the present study was to observe the effect of Astragali Radix Herbal-Acupuncture Solution(AR-HAS) at $ST_{36}$(jok-samni, $Z\acute{u}s\bar{a}n$ Li) on collagen- II -induced arthritis(CIA) in mice. Methods : DBA/1J mice were immunized with bovine type II collagen(CII) on days 0 and 21 to induce arthritis. The mice were divided into 5 groups : normal group(no CIA), control group(CIA+no treatment), needle prick group(CIA+single prick with an injection needle), saline group(CIA+saline injection) and ARHA group(CIA+ R-HA treatment). The needle prick, saline injection, and AR-HA groups were injected on the right $ST_{36}$(jok-samni) of mice for 9 weeks, 3 times a week, beginning 4 weeks after the booster immunization. Results : 1. The incidence of arthritis, AI(arthritis index), and joint edema decreased in the AR-HA group. 2. Weight gain, hypertrophy of the spleen, adhesion of the tissues, and transformation of the joint were restrained in the AR-HA group. 3. The concentrations of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $IFN-{\gamma}$ in CIA mouse serum and $IFN-{\gamma}$, IL-10 in the CIA mouse spleen cell culture decreased significantly at $ST_{36}$ in the AR-HA group. 4. Total cell counts increased significantly, and the ratio of $CD3e^+$ to $CD45R^+$, $CD4^+$ to $CD8^+$, and $CD4^+$ to $CD25^+$ cells decreased significantly at $ST_{36}$ in the CIA mouse spleen cell culture of the AR-HA group. 5. Total cell counts decreased significantly, and $CD4^+/CD25^+$ and $CD45R^+/CD69^+$ decreased significantly at $ST_{36}$ in the CIA mouse lymph nodes of the AR-HA group. 6. $CD3e^+/CD69^+$ and $CD11b^+/Gr-1^+$ cells decreased significantly at $ST_{36}$ in the CIA mouse joints of the AR-HA group. 7. The histological examination showed that cartilage destruction and synoviocyte proliferation decreased in the CIA mouse joints of the AR-HA group, and collagen fiber was expressed similar to that seen in the normal group. Conclusions : Our experiments show that at $ST_{36}$, an anti-inflammatory mechanism of AR-HA controls synovial cell proliferation and protects against cartilage destruction in rheumatoid arthritis.

• Journal of Life Science
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• v.14 no.5
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• pp.874-881
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• 2004

Angiogenesis has been implicated in progression of inflammation, arthritis, psoriasis, atherosclerosis as well as tumor growth and metastasis. Intensive studies have been carried out to develop a strategy for cancer treatment by blocking angiogenesis. During angiogenesis, endothelial proliferation and migration essentially occurs upon activation. In this study, we compared the expression profiles of human umbilical endothelial cells activated by incubating in vitro in the rich medium containing several growth factors, and non-activated ones. cDNA targets derived from total RNAs of HUVEC activated for 13 h in M199 medium containing endothelial cell growth supplement, 20% fetal bovine serum, and heparin, after reaching 70～80% confluency, or non-activated, were hybridized onto oligonucleotide microarrays containing 1,8864 genetic elements. Unsupervised hierarchical clustering analysis resulted in two subgroups on dendrogram exhibiting activated and non-activated HUVECs. We then extracted 122 outlier genes which were shown to be up-regulated or under-expressed by at least 2-folds in activated HUVECs. Among these, 32 annotated genes were up-regulated and 38 were down-regulated in activated HUVECs. Interestingly, genes involved in cell proliferation, motility, and inflammation/ immune response were up-regulated in activated HUVEC, whereas genes for cell adhesion or vessel morphogenesis/function were down-regulated. Unexpectedly, the expression of genes well-characterized as angiogenesis markers was not changed except Eph-B4, which was down-regulated about 4 folds. 52 unknown genes were also up- or down-regulated. Therefore, these results could provide an opportunity to targeting new vascular molecules for the development of anti-angiogenic molecules.

• Journal of Life Science
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• v.24 no.9
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• pp.1001-1005
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• 2014

Ginsenoside Rg3 is one of the active ingredients extracted from red ginseng, and it is an effective chemical component of the human body and well known in herbal medicine as a restorative agent. Several studies have shown that Rg3 has a potent anti-tumor effect on various cancer cell lines. However, Rg3-induced apoptosis in B16F10 melanoma cancer cells is not well understood. In the present study, we tested whether ginsenoside Rg3 could induce apoptosis in B16F10 melanoma cells. We found that Rg3 could inhibit B16F10 melanoma cell viability in a dose-dependent manner, but not normal cells, such as EA.hy.926 and NIH3T3 cells. We also found that Rg3 could induce apoptosis in B16F10 melanoma cells using tunnel-staining assay in a dose-dependent manner. Rg3 treatment induces the phosphorylation of p38 and the expression of Bax, but it inhibits the expressions of the phosphorylation of focal adhesion kinase Bcl2 and pro-caspase3. Taken together, our data suggest that Rg3 could be useful as an anti-cancer agent in B16F10 melanoma cells.