• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.391-398
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• 2018

The aim of this study was to evaluate the in vitro anti-inflammatory and utero-relaxant effect of ${\alpha}$-bisabolol on the pregnant human myometrium. Samples from the pregnant human myometrium were used in functional tests to evaluate the inhibitory effect of ${\alpha}$-bisabolol (560, 860, 1,200 and $1,860{\mu}M$) on spontaneous myometrial contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to ${\alpha}$-bisabolol in human myometrial homogenates were measured by ELISA. The anti-inflammatory effect of ${\alpha}$-bisabolol was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$) and interleukin $(IL)-1{\beta}$, and the anti-inflammatory cytokine IL-10, in pregnant human myometrial explants stimulated with lipopolysaccharide (LPS). Forskolin was used as a positive control to evaluate the cAMP and cytokine levels. ${\alpha}$-Bisabolol was found to induce a significant inhibition of spontaneous myometrial contractions at the highest concentration level (p<0.05). ${\alpha}$-Bisabolol caused a concentration-dependent decrease in myometrial cAMP levels (p<0.05) and a concentration-dependent decrease in LPS-induced $TNF{\alpha}$ and $IL-1{\beta}$ production, while IL-10 production did not increase significantly (p>0.05). The anti-inflammatory and utero-relaxant effects induced by ${\alpha}$-bisabolol were not associated with an increase in cAMP levels in pregnant human myometrial samples. These properties place ${\alpha}$-bisabolol as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.

• Herbal Formula Science
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• v.16 no.2
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• pp.101-114
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• 2008

Objective : The purpose of this study was to investigate the anti-inflammatory effects of Hwagae-san extract(HGSE) on the peritoneal macrophage. Methods : To evaluate anti-inflammatory effects of HGSE, We measured cytokines(interleukin-6; IL-6, interleukin-12; IL-12, tumor necrosis factor-${\alpha}$; TNF-${\alpha}$) and nitric oxide(NO) production in lipopolysaccharide(LPS)-induced macrophages. Furthermore, We examined molecular mechanism using western blot and also LPS-induced endotoxin shock. Results : 1. HGSE did not have any cytotoxic effect in the peritoneal macrophages. 2. HGSE reduced LPS-induced IL-6, TNF-${\alpha}$, IL-12 and NO production in peritoneal macrophages. 3. HGSE inhibited the activation of extracelluar signal-regulated kinase(ERK), C-Jun NH2-terminal kinase(JNK) but not of p38, degradation of IkB-${\alpha}$ in the LPS-stimulated peritoneal macrophages. 4. HGSE inhibited the production of TNF-$\alpha$, IL-6 and IL-12 in serum after LPS injection. Conclusion : These results suggest that HGSE may inhibit the production of TNF-${\alpha}$, IL-6, and IL-12 through inhibition of ERK and JNK activation, and that HGSE may be beneficial for inflammatory diseases.

• Korean Journal of Veterinary Research
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• v.51 no.3
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• pp.239-241
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• 2011

In this study, we investigated the kinetics of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6 and high mobility group box 1 (HMGB1) concentrations in a 48-h model of canine endotoxemia by lipopolysaccharide (LPS) injection. Four healthy beagles were slowly administered 1 mg/kg of LPS diluted in normal saline, while two others were administered normal saline as controls. Blood collection was performed at 0 h (baseline), 1 h and 3 h (for TNF-${\alpha}$), 6 h, 12 h, 24 h and 48 h of the experiment, and cytokine levels were determined using the sandwich ELISA method. Early increments of TNF-${\alpha}$ and IL-6 were observed (< 3 h), but HMGB1 levels increased the most at 12 h of the experiment and gradually decreased until 48 h. During the whole experiment, IL-6 and HMGB1 were sustained over 12 h of LPS injection, whereas TNF-${\alpha}$ decreased within 6 h of LPS injection. Taken together, canine HMGB1 levels increase relatively late (< 12 h) and sustained longer than TNF-${\alpha}$ and IL-6 in response to endotoxin. This is the first study to evaluate canine HMGB1 cytokine from endotoxemia in dogs.

• Korean Journal of Pharmacognosy
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• v.41 no.2
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• pp.97-102
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• 2010

Six triterpenoid compounds, friedelin (1), $3{\alpha}$-hydroxy-2-friedelanone (2), canophyllol (3), oleanolic aldehyde acetate (4), ursolic acid (5), and pachysandiol A (6) were isolated from the methylene chloride soluble fraction of the roots of A. japonica. The chemical structures of compounds 1-6 were determined by the basis of physico-chemical properties and spectroscopic methods such as 1D and 2D NMR. These compounds were isolated from this plant for the first time. For the isolated compounds (1-3), the inhibitory effect of IL-6 production in TNF-$\alpha$ stimulated MG-63 was examined. Among the isolates, $3{\alpha}$-hydroxy-2-friedelanone (2) showed potent inhibitory effect on IL-6 production in TNF-$3{\alpha}$ stimulated MG-63.

• International Journal of Oral Biology
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• v.39 no.1
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• pp.15-22
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• 2014

Aggregatibacter actinomycetemcomitans is an important pathogen in the development of localized aggressive periodontitis. Lipopolysaccharide (LPS) is a virulent factor of periodontal pathogens that contributes to alveolar bone loss and connective tissue degradation in periodontal disease. Our present study was designed to investigate the cytokine expression and signaling pathways regulated by A. actinomycetemcomitans LPS (Aa LPS). Cytokine gene expression profiling in RAW 264.7 cells was performed by microarray analyses. The cytokine mRNA and protein levels and related signaling pathways induced by Aa LPS were measured by RT-PCR, ELISA and western blotting. Microarray results showed that Aa LPS strongly induced the expression of NF-${\kappa}B$, NF-${\kappa}B$-related genes, inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in RAW 264.7 cells. NF-${\kappa}B$ inhibitor pretreatment significantly reduced the levels of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA and protein. In addition, the Aa LPS-induced TNF-${\alpha}$ and IL-$1{\beta}$ expression was inhibited by p38/JNK MAP kinase inhibitor pretreatment. These results show that Aa LPS stimulates TNF-${\alpha}$ and IL-$1{\beta}$ expression through NF-${\kappa}B$ and p38/JNK activation in RAW 264.7 cells, suggesting the essential role of this pathway in the pathogenesis of localized aggressive periodontitis.

• The korean journal of orthodontics
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• v.28 no.6 s.71
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• pp.915-926
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• 1998

The cytoskeleton has been shown to form a network, connecting the extracelluar matrix via integrin with the nucleus and the cytoplasmic constituents of the cell. It is therefore assumed that the cytoskeleton may mediate signals generated by perturbations originating in the matrix. The purpose of this study is to examine the effect of cytoskeletal change on osteoblastic cell activities. The author cultured osteoblastic cells obtained from neonatal mouse calvaria. The cells were teated with cytochalasin B(CB) or colchicine (COL) at four concentrations for 3 hours and after another 24 hours the conditioned media was collected and assayed for prostaglandin $E_2\;(PGE_2)$, interleukin-6(IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and matrix metalloproteinase-1(MMP-1). In addition, the cytoskeletal protein actin were observed by immuno-fluorescence. The results were as follows: 1. The production of $PGE_2$ showed the tendency to be increased in CB-treated group. $PGE_2$ was increased in COL-treated group dose-dependantly, 2. IL-6 production, in CB-treated group, was increased, except at 1.0 ${\mu}g/ml$. IL-6 was induced in COL-treated group. 3. TNF-$\alpha$ production was increased in CB-treated group, except at 1.0 ${\mu}g/ml$, and in COL-treated group, that was increased. 4. The MMP-1 production was decreased in CB-treated soup and was not changed in COL-treated group, which could be selectively visualized by immunoblotting with monospecific antibody. 5. The cytoskeletal actin stress fibers were disappeared and the cells showed to be rounded in CB-treated group. These results indicated that there are a relationship between the cytoskeletal rearrangements and osteoblastic cell activities, especially in release of paracrine/autocrine factors, such as $PGE_2$, IL-6, and TNF-$\alpha$.

• Parasites, Hosts and Diseases
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• v.51 no.1
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• pp.133-137
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• 2013

This study aimed to measure the levels of interferon-gamma (IFN-${\gamma}$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate ($NO_x$) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-1, IL-6, and $NO_x$. Cytokines were assessed by ELISA quantitative sandwich technique, and $NO_x$ was measured by the modified Griess method. Cytokine levels (IFN-${\gamma}$, TNF-${\alpha}$, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of $NO_x$ were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

• Tuberculosis and Respiratory Diseases
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• v.60 no.5
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• pp.554-563
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• 2006

Background: PM is known to induce various pulmonary diseases, including asthma, cancer, fibrosis and chronic bronchitis. Despite the epidemiological evidence the pathogenesis of PM-related pulmonary diseases is unclear. Methods: This study examined the effects of PM exposure on the secretion of $TNF-{\alpha}$ and $IL-1{\beta}$ in the cultured alveolar macrophages. The cultured primary alveolar macrophages were treated with the medium, PM ($5{\sim}20{\mu}g/cm^2$), LPS (5ng/ml), and PM with LPS for 24h and 48h respectively. ELISA was used to assay the secreted $TNF-{\alpha}$ and $IL-{\beta}$ in the culture medium. Western blotting was used to identify and determine the level of proteins isolated from the culture cells. The cells cultured in the $Lab-Tek^{(R)}$ chamber slides were stained with immunocytochemical stains. Results: PM induced $TNF-{\alpha}$ and $IL-1{\beta}$ secretion in the culturing alveolar macrophages, collected from the SPF and inflammatory rats. However, the effects were only dose-dependent in the inflammatory macrophages. When the cells were co-treated with PM and LPS, there was a significant synergistic effect compared with the LPS in the both cell types. Conclusion: PM might be play an important role in the induction and/or potentiation of various lung diseases by oversecretion of $TNF-{\alpha}$ and $IL-1{\beta}$.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.217-224
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• 2000

Background : It is well known that when macrophages are stimulated with endotoxin, they produce a wide variety of cytokine mediators, including TNF-$\alpha$ and IL-1$\beta$. However, there is an alteration in the macrophages' responsiveness when they are challenged with repeated bouts of endotoxin, termed "endotoxin tolerance" which is regarded as a self-protective phenomenon from continuous stimulation. In this study, endotoxin tolerance in the peripheral blood monocytes of sepsis patients was evaluated. Methods : Fourteen patients with organism-documented sepsis were included. The severity of illness was evaluated by APACHE II score. Peripheral blood monocytes were isolated from the patients and diluted to $1{\times}10^5$ well. After stimulation with endotoxin (LPS of E. coli O114 : B4, 100 ng/ml), they were incubated at $37^{\circ}C$ in 5% $CO_2$ incubator for 24 hours. Supernatant was collected for the measurement of TNF-$\alpha$ and IL-1$\beta$ with ELISA method. Peripheral blood monocytes of seven healthy volunteers were used as control. Results : The APACHE II score (mean$\pm$SD) of the patients at the time of blood sampling was 12.2$\pm$5.7. The primary infection foci were urinary tract infection, pneumonia, subacute bacterial endocarditis, and catheter related infection, etc. The causative organisms were gram negative rods (10 cases), gram positive cocci (6 cases) with two cases of mixed infection. Serum TNF-$\alpha$ could be measured in 4 cases with 29.9$\pm$27.7 pg/ml. Serum IL-1$\beta$was measurable in only one patient. The TNF-$\alpha$ level of supernatant of cultured peripheral blood monocytes was 2,703$\pm$2,066 pg/ml in patients and 2,102$\pm$1914 pg/ml in controls. The IL-1$\beta$level of supernatant was 884$\pm$1,050 pg/ml in patients and 575$\pm$558 pg/ml in controls. There was no difference of TNF-$\alpha$ and IL-1$\beta$ level between patients and controls. Conclusion : We cannot prove the phenomenon of endotoxin tolerance in this study. Future study needs to be focused on the more severe sepsis patients who were taken for sampling earlier. Addition of serum to the culture medium could be an another valuable option for the success of this study.

• Journal of Korean Neurosurgical Society
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• v.42 no.3
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• pp.200-204
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• 2007

Objective : Radiation therapy is an important treatment for brain tumor. However, serious complications such as radiation necrosis can occur and it may be secondary to the expression of acute phase genes, like cytokines. In particular, inflammatory cytokines (IL-$1{\beta}$, TNF-${\alpha}$) and other immunomodulatory cytokines (TNF-${\alpha}$, TGF-${\beta}1$) might be changed after irradiation (high single dose irradiation). Although it has been reported that IL-1 level is remarkably elevated within 8 week after the irradiation to the rat brain. the change of cytokines levels at acute phase (within 24 hours) has not been reported. In the present study, we examined TNF-${\alpha}$, TGF-${\beta}1$, and IL-$1{\beta}$ levels in acute phase to clarify the early effect of cytokines on the radiation-induced brain damage. Methods : Fifty Sprague-Dawley rats were used and these were divided into irradiation group and control group. After a burr-hole trephination on the right parietal area using a drill, a single 10Gy was irradiated at the trephined site. Their forebrains were extirpated at 30 min, 2 hr, 8 hr, 12 hr and 24 hr, respectively and examined for the expression of TNF-${\alpha}$, TGF-${\beta}1$, and IL-$1{\beta}$. Results : The expression of TNF-${\alpha}$ and TGF-${\beta}1$ were decreased until 12 hr after irradiation but elevated thereafter. The expression of IL-1 was peak at 8 hr and then decreased until 12 hr but elevated after this time window. The present study indicated that expression of cytokines (TNF-${\alpha}$, TGF-${\beta}1$ and IL-$1{\beta}$) were increased at 24 hr after the irradiation to the rat brain. IL-$1{\beta}$ level, on the other hand. reached peak at 8 hr after radiation injury. Conclusion : These findings indicate that IL-1, among various cytokines, may have a more important role in the inflammatory reaction by radiation injury at acute phase and provide some clues for better understanding of the pathogenesis of radiation injury.