• Journal of Applied Biological Chemistry
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• v.57 no.3
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• pp.205-210
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• 2014

Persicaria orientalis (L.) Spach (Po) and Potentilla fragarioides var. major Maxim (Pf) extracts were analyzed to investigate anti-inflammation through their suppressing effects on free radicals such as reactive oxygen species (ROS). In addition, with regard to Po and Pf, an analysis was conducted of their inhibitory effect on nitric oxide, which is produced in lipopolysaccharide (LPS)-treated murine macrophage RAW 264.7 cells, and their inhibitory effect on the translocation of the nucleus of nuclear factor-kappa B (NF-${\kappa}B$). The $IC_{50}$ value of ROS, which was induced by $50{\mu}M$ 3-morpholinosydnonimine hydrochloride (SIN-1), was found to be $23.35{\pm}1.27{\mu}g/mL$ due to the effect of the Po extract, and $8.46{\pm}1.22{\mu}g/mL$ due to the effect of the Pf extract. In addition, the $IC_{50}$ value of peroxynitrite treated with the Po extract was $2.19{\pm}0.04{\mu}g/mL$, whereas that of peroxynitrite treated with the Pf extract was $0.80{\pm}0.02{\mu}g/mL$. ROS and peroxynitrite were induced by $50{\mu}M$ 3-morpholinosydnonimine hydrochloride. There was an increase in the amount of nitric oxide in the RAW 264.7 cells treated with LPS ($1{\mu}g/mL$), whereas the level of NO was observed to significantly and dose-dependently decrease in the cells treated with Po and Pf. The amount of nitric oxide produced by the group treated with $10{\mu}g/mL$ of the Pf extract was $11.45{\pm}0.57{\mu}M$. Furthermore, the Po extracts inhibited the translocation of the nucleus of NF-${\kappa}B$ in LPS-treated RAW 264.7 cells. Therefore, it is highly possible that Po and Pf have anti-inflammatory properties.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.336-344
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• 2004

Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.152-159
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• 2005

Background : Exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with increased airway inflammation, and the $NF-{\kappa}B$ is known to be an indicator of cellular activation and of inflammatory mediator production. This study was undertaken to investigate the change of cytokine characteristics and $NF-{\kappa}B$ activity in induced sputum of COPD patients during exacerbation and recovery of the disease. Methods : Sputum induction was performed in 37 patients with COPD during exacerbation and during recovery and in 15 healthy subjects. Cell counts, levels of IL-6, IL-8 and $TNF-{\alpha}$ in induced sputum and NF-kB activity in macrophage of induced sputum were measured. Results : Patients with COPD showed significantly increased levels of IL-6, IL-8 and $TNF-{\alpha}$(p<0.01) and increased $NF-{\kappa}B$ activity in induced sputum(p<0.05) as compared with control subjects. Level of IL-8 during exacerbation of COPD decreased significantly during recovery(p<0.05). $NF-{\kappa}B$ activity and levels of IL-6 and $TNF-{\alpha}$ tended to be decreased during recovery, but not siginificantly. Conclusion : Activation of $NF-{\kappa}B$ and increased levels of IL-6, IL-8 and $TNF-{\alpha}$ were thought to be associated with pathogenesis and exacerbations of COPD.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.534-538
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• 2005

Purpose : Kawasaki disease(KD) is a multisystemic inflammatory vasculitis of unknown etiology. Many complications other than cardiovascular involvement have been recognized in KD. However, there have been few reports published concerning involvement of the lungs in this disease. The purpose of this study was to examine the relationship between serum TNF-${\alpha}$, the degree of coronary artery dilatation and chest X-ray(CXR) findings. In addition, we have investigated serum anti-Mycoplasma antibody(AMA) titers in patients with KD who have abnormal CXR findings. Methods : Eighty four patients with KD were included in this study(group I; 41 patients with normal CXR fndings, group II; 43 patients with abnormal CXR findings). Serum levels of TNF-${\alpha}$ and AMA titer were measured. Results : We reviewed the CXR findings and clinical courses of 84 patients with Kawasaki disease and found abnormal CXR findings in 43 patients(51.2 percent). Peribronchial cuffing was the most frequent abnormality(22.4 percent). In the group with abnormal CXR findings(group II), a statistical difference was not noted in age, sex, duration of fever, hemoglobin, WBC, platelet, ESR, and CRP levels and incidence of coronary arterial lesions as compared with the group having normal CXR findings(group I). No difference was noted in serum TNF-${\alpha}$ level between group I and group II. 2 patients(12.5 percent) of 16 KD patients with abnormal CXR findings have positive AMA titer(above 1 : 320). Conclusion : Most of the abnormal CXR findings in KD patients were peribronchial cuffing. The abnormal CXR findings in KD patients did not mean severe inflammations. It is difficult to consider that CXR abnormalities are related to coronary arterial lesions. In addition, further study on the relationship between Mycoplasma infection and Kawasaki disease is needed.

• Journal of Nutrition and Health
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• v.53 no.5
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• pp.452-463
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• 2020

Purpose: Aster tataricus (AT) is one of the Asteraceae perennial herbs used in traditional Chinese medicine. The herb contains various bioactive substances, such as flavonoids, isoflavonoids, and phenolic compounds in the roots, and exhibits a range of effects including anti-bacterial, anti-oxidant, and anti-inflammatory activities. This study compared the immunomodulatory effects of ethanol and water extracts of whole AT, except the roots, and analyzed the molecular mechanisms for the regulatory effects on cytokine secretion from THP-1 cells. Methods: The effects of AT extract on the cell viability and proliferation of THP-1 cells were analyzed using the Cell Counting Kit-8 method. The concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant of the AT-treated THP-1 cells were measured using an enzyme-linked immunosorbent assay. The protein levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor kappa B (IκBα), and mitogen-activated protein kinase (MAPK) phosphorylation in the cell lysates were determined by western blotting. Results: The water extract and the ethanol extract of AT did not affect the cell viability, and increased the proliferation of THP-1 cells significantly compared to the vehicle. The water extract increased the secretion of IL-1β from THP-1 cells in a dose-dependent manner, but the ethanol extract had no effect. The expression of COX-2 and iNOS protein and the phosphorylation of MAPK and Akt were induced in AT-treated cells. In addition, IκBα was degraded by AT in a concentration-dependent manner. IL-1β secretion by AT was reduced by extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors, while TNF-α secretion was decreased by inhibitors of ERK, p38 MAPK, and JNK. Interestingly, the p38 MAPK inhibitor increased the production of IL-1β by AT further. Conclusion: The water extract of the above-ground parts of AT contains immunomodulatory bioactive substances that stimulate immune cells through the MAPK signaling pathway.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.51-64
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• 2002

We have compared(using the same series of experimental tissue samples) the levels of proteolytic enzyme activities and free radical-induced protein damage in synovial fluid from RA and CPH cases. Many protease types showed significantly increased (typically by a factor of approximately 2-3-fold) activity in RA, compared to normal rats. However, CPH significantly reduced the cytoplasmic enzyme activities of arginyl aminopeptidase, leucyl aminopeptidase, pyroglutamyl aminopeptidase, tripeptidyl aminopeptidase, and proline endopeptidase to almost about 1/10 each. For the Iysosomal proteases, synovial fluid samples from RA rats, CPH significantly reduced the enzyme activities of cathepsin B, dipeptidyl aminopeptidase I and dipeptidyl aminopeptidase II. In extracellular matrix degrading(collagenase, tissue elastase) and leukocyte as sociated proteases (leukocyte elastase, cathepsin G), CPH decreased these enzyme activities of collagenase, tissue elastase and leukocyte associated elastase in RA. In cytoplasmic and lysosomal protease activities in plasma from RA. CPH and normal plasma samples were not significantly different, suggesting that altered activity of plasma proteases (particularly those enzymes putatively involved in the immune response) is not a contributory factor in the pathogenesis of RA. In addition, the level of free radical induced damage to synovial fluid proteins was approximately twice that in RA, compared with CPH. CPH significantly decreased the level of ROS induced oxidative damage to synovial fluid proteins (quantified as protein carbonyl derivative). Therefore we conclude that both proteolytic enzymes and free radicals are likely to be of equal potential importance as damaging agents in the pathogenesis of inflammatory joint disease, and that the design of novel therapeutic strategies for patients with the latter disorder should include both protease inhibitory and free radical scavenging elements. In addition, the protease inhibitory element should be designed to inhibit the action of a broad range of protease mechanistic types (i.e. cysteine-, metallo- and serine- proteinases and peptidases). However, increased protein damage induced by ROS could not be rationalised in terms of compromised antioxidant total capacity, since the latter was not significantly altered in RA synovial fluid or plasma compared with CPH.

• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.199-210
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• 2003

Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.

• Journal of Chest Surgery
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• v.40 no.3 s.272
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• pp.180-192
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• 2007

Background: As determined from the recent investigations of discordant cardiac xenotransplantation, hyperacute rejection occurs mainly at the endothelial cells in donor microvascular systems, but this does not occur at cardiac valve leaflets or at medium-to-large caliber vessels. On the basis of this background, this study was performed to look into the biocompatibility for transplantation of a middle or large diameter xenogenic blood vessel by conducting xenogenic arterial transplantation with the carotid artery in a pig-to-goat model. Material and Method: The experimental group was composed of 10 pairs of pig-to-goat combinations. They were divided into each period of 1 week, and 1, 3, 6 and 12 months. Four carotid artery grafts obtained through collection of the bilateral carotid arteries from two pigs were preserved at $-70^{\circ}C$ without other treatment, and then they were transplanted into the bilateral carotid arteries of two goats. Doppler ultrasonography was done on a periodic basis after transplantation to evaluate the patency of the grafted blood vessel. At the ends of a predetermined period, the grafts were explanted from the goats and they underwent gross examination. Hematoxylin-eosin and Masson's trichrome staining were conducted. In addition, in order to examine the immunological rejection of the grafted xenogenic blood vessel, immunohistochemical staining was conducted with T-lymphocyte indicator and von Willebrand factor. Result: Two goats at the each one-week period and the one-year period died during the experimental period because of a reason unrelated to the experimental procedure, and the remaining 8 goats survived until the end of each experiment period. On Doppler ultrasonography, unilateral carotid artery occlusion was found in a goat, whose period was specified as 3 months, among the 8 survived goats. However, the vascular patency was maintained well and there was no graft that formed aneurysms in the other goats. On gross examination, the region of vascular anastomosis was preserved well, and calcification of the grafted blood vessel was not shown. Histologically, the endothelial cells of the graft disappeared one week after transplantation, and then there was progressive spread of the recipients' endothelial cells from the anastomotic site. The reendothelialization occurred over the whole graft at one month after transplantation. The neointimal thickening and adventitial inflammation became severe by 3 months after transplantation, but this lessened at 6 months and 12 months, respectively. The rate of CD3 positive cells was very low among the infiltrated inflammatory cells. Conclusion: The fresh-frozen xenogenic artery kept its patency without being greatly influenced by xenogenic immune reaction.

• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

• Journal of Life Science
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• v.25 no.6
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• pp.693-702
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• 2015

Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.