• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.1-14
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• 1982

The effects of xanthine-xanthine oxidase reaction on brain microsomal $Na^+-K^+-ATPase$ activity were studied to see possible involvement of oxygen free radicals in pathologic change occurring in ischemic state of CNS accompanied by cerebral vascular occlusion or impact injury. When microsomal fraction was incubated with xanthine ana xanthine oxidase, $Na^+-K^+-ATPase$ activity of the fraction was markedly inactivated (80% inactivation) whereas btssl $Mg^{++}-ATPase$ was much less sensitive (less than 10% inactivation) compared to that of $Na^+-K^+-ATPase$. The inactivation was observed only in the presence of both xanthine and xanthine oxidase, not either of them alone, and the extent of inactivation was dependent on the concentration of xanthine. In an attempt to determine which of the oxygen species was responsible for the inactivation, the ability of various scavengers to overcome the inactivation was tested. Superoxide dismutase, catalase and 1,4-diazabicyclo(2,2,2)octane were shown to reverse the inactivation of the ATPase in dose-dependent manner. In contrast, mannitol as well as other $OH{\cdot}$quenchers were ineffective in limiting oxygen radical-induced inactivation. Thus $O_{\bar{2}}{\cdot},\;H_2O_2$ and $^1O_2$ were implicated to be mediators involved in the inactivation. Since oxygen radicals are suspected as being a cause of the peroxidative damaging process in train ischemia, the ATPase inactivation by oxygen radicals may be a possible contributing factor which gives rise to functional derangement of nerve cells observed in the pathologic process.

• Food Science and Preservation
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• v.22 no.4
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• pp.613-621
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• 2015

In this study, the anti-oxidant and anti-inflammatory activities of water extract (ASSW) and 70% ethanol extract (ASSE) of Allium sativum L. stems were investigated using Raw 264.7 cells induced by lipopolysaccharide (LPS). ABTS radical scavenging activities of ASSW and ASSE at $1000{\mu}g/mL$ concentration were 96.9% and 97.8%, respectively. In order to investigate the potential anti-inflammatory effects of ASSW and ASSE, nitric oxide (NO), pro-inflammatory cytokines, interleukin-6 (IL-6), and tumor necrosis factor including ${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and prostaglandin-E2 (PGE2) were measured. ASSW and ASSE at $100{\mu}g/mL$ concentration showed inhibitory effects against NO production by 18% and 23%, respectively. Production of IL-$1{\beta}$ and IL-6 after treatment with ASSW and ASSE at $100{\mu}g/mL$ decreased by approximately 28% and 15% for ASSW and 17% and 12% for ASSE, respectively. In addition, production of TNF-${\alpha}$ after treatment of $100{\mu}g/mL$ of ASSW and ASSE decreased by 24% and 23%, respectively. In addition, the treatment of $100{\mu}g/mL$ of ASSW and ASSE showed inhibitory expressions against PGE2 by 45.47% and 33.87%, respectively. These results suggested that ASSE showed greater inhibitory activity than that of the ASSW by the suppression of inflammatory mediators, including NO, IL-6, TNF-${\alpha}$ and PGE2 production, and the expressions of iNOS and COX-2 in macrophages. In conclusion, ASSW and ASSE may have some ancillary effects on inflammatory factors as potential anti-inflammatory agents.

• Food Science and Preservation
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• v.23 no.3
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• pp.378-386
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• 2016

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.

• The korean journal of orthodontics
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• v.28 no.4 s.69
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• pp.611-626
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• 1998

Cytokines are intercellular peptide mediators that regulate homeostasis and host defense reactions in living body. Of the diversity of cytokines in terms of biological accomplishment, interleukin $1-{\beta}$($IL-1{\beta}$) and tumor necrosis factor(TNF) are the most conspicuous cytokines with a wide variety of effects on cells involved in inflammatory and immune responses, and likely to be involved in the inflammatory pathogenesis of oral tissue as well. The present study was designed to explicate the role of $IL-1{\beta}$ on inflammatory revelation of oral tissues in mice biochemically. In the Induced arthritis by injection of 10${\mu}g$ LPS shown the relaese of 0.93 ${\mu}g$ $IL-1{\beta}$/joint with a peak at at 4-5 h. and diminished at 24t and the release of $TNF_{\alpha}$ of 1.25 ${\mu}g$/joint with a peak at 2-3h and diminished at 6h. After injection of th $IL-1{\beta}$ into the joint, the mumber of leucocytes proliferated with a peak at 4-5h and diminished at 36h and the loss of proteoglycan showed with maximum at 15-30h. After injection of $IL-1{\beta}$ into the oral tissue, cycloosygenase metabolites ($PGE_2$) accumulated in the oral tissue with dose dependant. These elucidated $IL-1{\beta}$ to be inflammatory mediator in the early phase of its pathogenesis. Intraoral injection of recombinant $IL-1{\beta}$ induced the proliferation of leukocytes in situ. $IL-1{\beta}$ took an pertinent part in the development of inflammation and the succession of cellular infiltration. The results exemplify that $IL-1{\beta}$ plays a significant role in mediating inflammatory response induced by LPS in oral tissue, the inflammatory response is regulated by $IL-1{\beta}$ at an acute phase of pathogenesis.

• Tuberculosis and Respiratory Diseases
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• v.39 no.3
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• pp.228-235
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• 1992

Background: Although polymorphonuclear leukocytes (PMN) are important in protecting the airways and alveolar surfaces, there is evidence that they can also injure the lung while exercising their defensive role. However it has been unclear whether PMN-induced pneumocyte injury is mediated by their direct cytotoxic effect on target cells or by PMN-derived cytotoxic mediators. On the other hand histamine was known not only to act as an important chemical mediator participated in the pathogenesis of some atotic and allegic disorders, but also to have an inhibitory effect on normal PMN functions. Method: To study the mechanism by which PMN induce pneumocyte injury, we cocultured PMN from four healthy nonsmokers or their PMN-derived supernatants (PMN-SPN) with monolayers of $^{51}Cr$-labeled human A549 pneumocytes and compared PMN-and PMN-SPN-mediated pneumocyte injuries measured by $^{51}Cr$ release assay. We also compared the effects of histamine on each pneumocyte injury. Results: 1) PMN-SPN showed more injurious effect on A549 pneumocytes than that of PMN itself regardless histamine pretreatment of PMN. 2) Pneumocyte injury by PMN with histamine pretreatment was increased or decreased compared with that by PMN without histamine pretreatment, according to histamine concentrations, and PMN stimulating agents and their concentrations. 3) Pneumocyte injury by PMN-SPN with histamine pretreatment tended to be decreased compared with that by PMN-SPN without histamine pretreatment. Conclusion: Our results suggest that PMN-SPN may play more important role in mediating pneumocyte injury than PMN itself and that histamine may partially play a protective role on PMN-induced pneumocyte injury. Alternatively we conclude that the effects of histamine on PMN-induced pneumocyte injury may be affected by microenvironment in vivo.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.219-229
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• 2002

Background : Sepsis-induced acute lung injury (ALI) is caused by many cellular and humoral mediators induced by an endotoxin. Histamine, which is widely distributed in the lungs and has been considered as an important mediator of sepsis. It increases P-selectin expression on the endothelial cell surfaces and induces IL-8 secretion. Therefore, an endotoxin-induced histamine may be related to neutrophil-mediated ALI by inducing the migration and activation of neutrophils in the lung tissue. However, the role of endogenous histamine in endotoxin ALI has not been clarified. The purpose of this study was to investigate how endotoxin-induced ALI is influenced by endogenous histamine and to identify the possible mechanism of action. Materials and Methods : The study consisted of 4 groups using Sprague-Dawley rats : 1) control group, where the rats were infused intratracheally by normal saline, 2) an endotoxin group, where lipopolysaccharide (LPS) was administered intratracheally 3) the $H_2$ receptor antagonist-treated group ($H_2$ group) and 4) the $H_1$ receptor antagonist-treated group ($H_1$ group), where $H_2$-receptor blocker (ranitidine) and $H_1$-receptor blocker(pyrilamine) were co-treated intravenously with the intratracheal administration of an endotoxin. The lung leak index using $I^{125}$-BSA, the total protein and LDH concentration in the lung lavage fluid, myeloperoxidase(MPO) activity in the lung tissue, the pathologic score and the total number of neutrophils, TNF-$\alpha$, IL-$1{\beta}$ and IL-10 in lung lavage (BAL) fluid were measured in each group as the indices of lung injury. Results : Compared to the control group, the endotoxin group exhibited significant increases in all lung injury indices. Significant reductions in the endotoxin-mediated increases in lung leak index (p<0.05) were observed in both the $H_1$ and $H_2$ groups. In addition the total protein (p<0.05) and LDH concentration (p<0.05) in the BAL fluid were also lower in the $H_2$ group compared to the endotoxin group. However, there was no change in the MPO activity in the lung tissue, the pathologic score and the total number of neutrophils in the BAL fluid in both the $H_2$ and $H_1$ groups compared to the endotoxin group. The increases in TNF-$\alpha$ IL-$1{\beta}$ and IL-10 concentrations in the BAL fluid observed in the endotoxin group were not reduced in the $H_2$ and $H_1$ groups. Conclusion : Antihistamine attenuated the enhanced alveolar-capillary permeability induced by the endotoxin via the $H_2$ receptor. However the attenuating mechanism may not be related to the pathogenesis of neutrophil dependent lung injury.

• Tuberculosis and Respiratory Diseases
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• v.67 no.2
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• pp.95-104
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• 2009

Background: The pathophysiologic mechanisms of early acute lung injury (ALI) differ according to the type of primary insult. It is important to differentiate between direct and indirect pathophysiologic pathways, and this may influence the approach to treatment strategies. NF-$\kappa$B decoy oligodeoxynucleotide (ODN) is a useful tool for the blockade of the expression of NF-$\kappa$B-dependent proinflammatory mediators and has been reported to be effective in indirect ALI. The purpose of this study was to investigate the effect of NF-$\kappa$B decoy ODN in the lipopolysaccharide (LPS)-induced direct ALI model. Methods: Five-week-old specific pathogen-free male BALB/c mice were used for the experiment. In the preliminary studies, tumor necrosis factor (TNF)-$\alpha$, interleukine (IL)-6 and NF-$\kappa$B activity peaked at 6 hours after LPS administration. Myeloperoxidase (MPO) activity and ALI score were highest at 36 and 48 hours, respectively. Therefore, it was decided to measure each parameter at the time of its highest level. The study mice were randomly divided into three experimental groups: (1) control group which was administered 50 ${\mu}L$ of saline and treated with intratracheal administration of 200 ${\mu}L$ DW containing only hemagglutinating virus of Japan (HVJ) vector (n=24); (2) LPS group in which LPS-induced ALI mice were treated with intratracheal administration of 200 ${\mu}L$ DW containing only HVJ vector (n=24); (3) LPS+ODN group in which LPS-induced ALI mice were treated with intratracheal administration of 200 ${\mu}L$ DW containing 160 ${\mu}g$ of NF-$\kappa$B decoy ODN and HVJ vector (n=24). Each group was subdivided into four experimental subgroups: (1) tissue subgroup for histopathological examination for ALI at 48 hours (n=6); (2) 6-hour bronchoalveolar lavage (BAL) subgroup for measurement of TNF-$\alpha$ and IL-6 in BAL fluid (BALF) (n=6); (3) 36-hour BAL subgroup for MPO activity assays in BALF (n=6); and (4) tissue homogenate subgroup for measurement of NF-$\kappa$B activity in lung tissue homogenates at 6 hours (n=6). Results: NF-$\kappa$B decoy ODN treatment significantly decreased NF-$\kappa$B activity in lung tissues. However, it failed to improve the parameters of LPS-induced direct ALI, including the concentrations of tumor necrosis factor-$\alpha$ and interleukin-6 in BALF, myeloperoxidase activity in BALF and histopathologic changes measured by the ALI score. Conclusion: NF-$\kappa$B decoy ODN, which has been proven to be effective in indirect models, had no effect in the direct ALI model.

• Journal of Periodontal and Implant Science
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• v.26 no.4
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• pp.949-965
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• 1996

The main goal of periodontal therapy is to restore the lost periodontal tissue and establish the attachment appratus. Current acceptable therapeutic techniques are included : removal of diseased soft tissue, demineralization of exposed root surface, using the barrier membrane for preventing the downgrowth of gingival epithelial cell, insertion of graft materials as a scaffolding action, and biological mediators for promoting the cell activity. The latest concept one among them has been studied which based on the knowledge of cellular biology of destructed tissue. Platelet-derived growth factor(PDGF) is one of the polypeptide growth factor which have been reported as a biological mediator to regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the influences of the PDGF as biological mediator to periodontal ligament and bone marrow cell. Both right and left maxillary first molar were extracted from rat which had treated with 0.4% ${\beta}-Aminopropionitril$ for 5 days, and feeded until designed date to sacrifice under anesthesisa. Periodontal ligament were removed from the extracted socket of the rat, and cultured with Dulbecco's Modified Essential Medium(DMEM) contained with 10% Fetal Bovine Serum, 100U/ml penicillin, $100{\mu}g/ml$ streptomycin, $0.5{\mu}g/ml$ amphotericin-B. Bone marrow cell were culture from bone marrow suspension with which washed out from femur with same medium. The study was performed to evaluate the effect of PDGF to periodontal ligament and bone cell, cell proliferation rate, total protein synthesis, and alkaline phosphatase activity of rat periodontal ligament(PDL) cell and bone stromal(RBS) cell in vitro. The effects of growth factors on both cells were measured at 3, 5th day after cell culture with (control group) or without growth factors(experimental group). The results were as follows: 1. The tendency of cell proliferation under the influence of PDGF showed more rapid proliferation pattern than control at 3 and 5 days after inoculation. 2. The activity of Alkaline phosphatase revealed 14, 80% increased respectively at 3, 5 days culture than control group. Measurements of ALPase levels indicated that PDL cells had significantly higher activity when compared with that of co-culture groups and GF only(P<0.05). And, ALPase activity in 10 days was higher than that of 7 days(P<0.05). 3. The tendency of formation of the mineralized nodule were observed dose-depend pattern of PDL cells. There was statistically significant difference among group l(PDL 100%), 2(PDL 70%:GF 30%), and 3(PDL 50%:GF 50%)(P<0.01). But, there was no difference among group 3, 4(PDL 30%:GF 70%), and 5(GF 100%). 4. Also, the number of nodule was greater in co-culture of PDL 70% and GF 30% than in culture of PDL 70%(P<0.05). From the above results, it is assumed that the PDGF on PDL cells and RMB cell culture. GF stimulates the cell growth, which is not that of PDL cells but GF. And, the activity of ALPase depends on the ratio of PDL cells, and ALPase may relate to the initial phase of nodule formation. Also, it is thought that the calcified nodule formation principally depends on PDL cells, is inhibited by GF, and affected by cell density. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1552-1559
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• 2013

Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.462-474
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• 1994

Background : In acute lung injury, activated neutrophils play an important role in tissue damage. For neutrophils to participate in lung inflammation, chemotactic factors released from mononuclear phagocytes are needed to bring these cells to the local site of inflammation, with interleukin-8 (IL-8) being one of the most specific and important chemotactic factors for neutrophils. IL-8 also induces the expression of adhesion molecules and activates neutrophils to release various inflammatory mediators. Lipopolysaccharide(LPS) is one of the most important causes of adult respiratory distress syndrome and can cause release of many inflammatory cytokines including IL-8 leading to acute lung injury. But little is known about the regulatory mechanism of LPS-induced IL-8 gene expression in mononuclear phagocytes. Method : Human alveolar macrophages(HAM) and peripleral blood monocytes(PBMC) were isolated from healthy volunteers. Time and dose relationship of LPS-induced IL-8 mRNA expression was observed by Northern blot analysis. To evaluate the regulatory mechanism of LPS-induced IL-8 gene expression, pretreatment of actinomycin D(AD, $5{\mu}g/ml$) and cycloheximide(CHX, $5{\mu}g/ml$) was done and Northern blot analysis for IL-8 mRNA and ELISA for immunoreactive IL-8 protein in culture supernatant were performed. Results : 1) In HAM, dose and time dependent LPS-induced IL-8 mRNA expression was observed with peak mRNA level at 8 hours post-stimulation. 2) In PBMC, dose and time dependent LPS-induced IL-8 mRNA expression was also observed with peak mRNA level at 4 hours post-stimulation. 3) AD decreased expression of LPS-induced IL-8 gene expression at both mRNAand protein levels in both types of cells. 4) CHX decreased expression of LPS-induced IL-8 gene expression at protein level in both cell types but in HAM, superinduction of IL-8 mRNA was observed while decreased expression of IL-8 mRNA was observed in PBMC. Conclusion : Time and dose dependent LPS-induced IL-8 gene expression was observed in mononuclear phagocytes which is at least partly regulated pretranslationally. LPS-induced IL-8 mRNA expression in HAM needs no de novo protein synthesis and may be under the control of a labile repressor protein while de novo protein synthesis may be needed in PBMC.