• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.37-45
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• 2002

Background: Diffuse panbronchiolitis(DPB) is a chronic inflammatory lung disease that presents as coughing, copious sputum, exertional dyspnea, which progresses to bronchiectasis. The pathogenesis of bronchiectasis is controlled by inflammatory mediators, which are closely related to mucus hypersecretion, goblet cell dysplasia. In recent studies, the epidermal growth factor receptor(EGFR) system was reported to be associated with this process. It was hypothesized that a relationship exists between goblet cell dysplasia, EGFR expression, and inflammatory mediators produced by neutrophil. Method: Alcian blue/periodic acid -Schiff(AB/PAS) stain, MUC5AC, EGFR, CD16 immunohistochemical stain were examined to investigate a role for the EGFR system in a mucus hypersecretion in DPB using the lung biopsy specimens from 13 DPB patients and 6 controls. Results : In the DPB group, the AB/PAS and MUC5AC -stained areas were $8.31{\pm}3.36%$, $11.46{\pm}4.68%$, respectively. In the control group, the AB/PAS- and MUC5AC-stained areas were $50.5{\pm}5.77%$, $53.3%{\pm}6.67%$, which was significantly larger than in the DPB group (each comparison, p<0.05). The percentage of EGFR expression was $9.54{\pm}4.95%$ in the DPB group, but zero in of the control group. The extent of neutrophilic infiltration was $71.92{\pm}3.71$/5HPF in the DPB group and $45.0{\pm}5.73$/5HPF in the control group, which was statistically significant(p=0.002). Conclusion: The EGFR system is highly related to goblet cell dysplasia, mucus hypersecretion and neutrophilic inflammation in DPB.

• Journal of Nutrition and Health
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• v.55 no.2
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• pp.227-239
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• 2022

Purpose: This study investigated the effects of water-soluble mulberry leaf extract (ME) on hepatic lipid accumulation in high-fat diet-fed rats via the regulation of hepatic microRNA (miR)-221/222 and inflammation. Methods: Male Sprague-Dawley rats (4 weeks old) were randomly divided into 3 groups (n = 7 each) and fed with 10 kcal% low-fat diet (LF), 45 kcal% high-fat diet (HF), or HF + 0.8% ME for 14 weeks. Lipid profiles and cytokine levels of the liver and serum were measured using commercial enzymatic colorimetric and enzyme-linked immunosorbent assay, respectively. The messenger RNA (mRNA) and miR levels in liver tissue were assayed by real-time quantitative reverse-transcription polymerase chain reaction. Results: Supplementation of ME reduces body weight and improves the liver and serum lipid profiles as compared to the HF group. The mRNA levels of hepatic peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, fatty acid synthase, and fatty acid translocase, which are genes involved in lipid metabolism, were significantly downregulated in the ME group compared to the HF group. In contrast, the mRNA level of hepatic carnitine palmitoyl transferase-1 (involved in fatty acid oxidation) was upregulated by ME supplementation. Furthermore, administration of ME significantly downregulated the mRNA levels of inflammatory mediators such as hepatic tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The serum levels of TNF-α, IL-6, and nitric oxide were also significantly reduced in ME group compared to the HF group. Expression of hepatic miR-221 and miR-222, which increase in the inflammatory state of the liver, were also significantly inhibited in the ME group compared to the HF group. Conclusion: These results indicate that ME has the potential to improve hepatic lipid accumulation in high-fat diet-fed rats via modulation of inflammatory mediators and hepatic miR-221/222 expressions.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.332-342
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• 2000

Background : The importance of pro-inflammatory cytokines, especially tumor necrosis factor $\alpha$ (INF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$), have been extensively documented in the generation of inflammatory lung disease. Lung epithelial cells are also actively involved in initiating and maintaining inflammation by producing pro-inflammatory mediators. Understanding the mechanism of pro-inflammatory cytokine expression in lung epithelial cells is crucial to the development of new therapeutic modalities for inflammatory lung disease. Transcription of most pro-inflammatory cytokines is dependent on the activation of NF-${\kappa}B$. However, the relationship between pro-inflammatory cytokine expression and NF-${\kappa}B/I{\kappa}B$ pathway in lung epithelial cells is not clear. Methods : BEAS-2B, A549, Na-H157, NCI-H719 cells were stimulated with IL-$1{\beta}$ or TNF-$\alpha$ at various times, and then IL-8 and TNF-$\alpha$mRNA expressions were assayed by Northern blot analysis. IL-$1{\beta}$ or TNF-$\alpha$-induced NF-${\kappa}B$ activation was assessed by the nuclear translocation of p65 NF-${\kappa}B$ subunit. The degradation of $I{\kappa}B{\alpha}$ and $I{\kappa}B{\beta}$ by IL-$1{\beta}$ or TNF-$\alpha$stimulation was assayed by Western blot analysis. The phosphorylation of $I{\kappa}B{\alpha}$ was evaluated by Western blot analysis after pre-treating cells with proteasome inhibitor followed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation. The basal level of IKK $\alpha$ expression was evaluated by Western blot analysis. Results: $I{\kappa}B{\alpha}$ and $I{\kappa}B{\alpha}$ was rapidly degraded after 5 minutes of incubation with IL-$1{\beta}$ or TNF-$\alpha$ in BEAS-2B, A549, and NCI-H157 cells. The activation of NF-${\kappa}B{\alpha}$ and the induction of IL-8 and TNF-$\alpha$ mRNA expression were observed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in these cells. In contrast, neither the changes in NF-${\kappa}B/I{\kappa}B$ pathway nor IL-8 and TNF-$\alpha$mRNA expression was induced by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in NCI-H719 cells. IL-$1{\beta}$ and TNF-$\alpha$-induced $I{\kappa}B$ phosphorylation was observed in BEAS-2B, A549, and NCI-H157 cells, but not in NCI-H719 cells. The basal level of IKK$\alpha$ expression was not different between cell. Conclusion : NF-${\kappa}B/I{\kappa}B$ pathway plays an important role in the expression of pro-inflammatory cytokine in most lung epithelial cells. The absence of the effect on NF-${\kappa}B/I{\kappa}B$ pathway in NCI-H719 cells sæms to be due to the defect in the intracellular signal transduction pathway upstream to IKK.

• Journal of Life Science
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• v.28 no.2
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• pp.207-215
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• 2018

Inflammatory response and oxidative stress play critical roles in the development and progression of many human diseases. Therefore, a great deal of attention has been focused on finding functional materials that can control inflammation and oxidative stress simultaneously. The purpose of this study was to investigate the effects of Socheongja and Socheong 2, Korean black seed coat soybean varieties, on the inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our data indicated that the extracts of Socheongja (SCJ) and Socheong 2 (SC2) significantly suppressed LPS-induced production of nitrite oxide (NO) and prostaglandin $E_2$, key pro-inflammatory mediators, by suppressing the expression of inducible NO synthase and cyclooxygenase-2. It was also found that SCJ and SC2 reduced the LPS-induced secretion of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$, which was concomitant with a decrease in the protein levels. In addition, SCJ and SC2 markedly diminished LPS-stimulated intracellular reactive oxygen species accumulation, and effectively enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression. Furthermore, LPS-induced activation of mitogen-activated protein kinases (MAPKs) was abrogated by SCJ and SC2. Taken together, these data suggest that SCJ and SC2 may offer protective roles against LPS-induced inflammatory and oxidative responses in RAW 264.7 macrophages through attenuating MAPKs pathway, and these effects are mediated, at least in part, through activating Nrf2/HO-1 pathway. Given these results, we propose that SCJ and SC2 have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by over-activation of macrophages.

• 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.

• Food Science and Preservation
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• v.23 no.6
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• pp.876-882
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• 2016

The antioxidant and anti-inflammatory effects of Corni fructus extracts (CEF, EtOAc extraction; CBF, buthanol extraction; CWF, water extraction) were investigated. The total phenolics of CEF (173.3 mg TAE/g) were significantly higher than those of CWF (26.7 mg TAE/g) and CBF (94.8 mg TAE/g). DPPH and ABTS free radical scavenging activity of CEF (DPPH: $RH_{50}$; $25.1{\mu}g/mL$, ABTS: $RC_{50}$; $36.1{\mu}g/mL$) showed even higher than that of BHA and ${\alpha}-tocopherol$ used as positive control. All three Corni fructus extracts in the concentration of $1{\sim}100{\mu}g/mL$ were effective inhibitors of NO and prostaglandin $E_2$ ($PGE_2$). NO production was inhibited 71.3~92.2% by CEF, 76.8~85.5% by CBF and 74.4~96.9% by CWF, respectively. CEF, CBF and CWF ($1{\sim}100{\mu}g/mL$) inhibited also pro-inflammatory cytokines like $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 very effectively. $TNF-{\alpha}$ was inhibited up to 51.2% by CWF and $IL-1{\beta}$ was inhibited up to 67.1% by CEF. IL-6 was best inhibited by CEF up to 58.9%. This study suggested the potential of Corni fructus for use as an excellent antioxidant substance and inflammatory inhibiting mediators. Therefore CEF, CBF and CWF Corni fructus extracts may be used for therapeutic approach to various inflammatory diseases.

• Tuberculosis and Respiratory Diseases
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• v.50 no.3
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• pp.300-309
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• 2001

Background : Sepsis is a clinical syndrome characterized by a systemic inflammatory and hemodynamic response to severe bacterial infections that involve various mediators. Endothelin (ET)-1, a potent vasoconstrictor is associated with mu1tiple organ failure, and interleukin (IL)-8, a proinflammtory cytokine, plays a major role in neurophil activation. Both have been reported to be useful parameters in the clinical assessment of sepsis. The levels of ET-1 and IL-8 in the blood were measured in patients with sepsis, and the correlation of both parameters and their relationship with the clinical data was assessed. Methods : 19 sepsis patients and 17 controls were studied. Blood samples of the sepsis patients were drawn in day 1, 3, 7, and 14. The APACHE III scores were calculated in concurrent days. The ET-1 and IL-8 levels were measured using immunoassay methods. Results : The ET-1 levels of patients with sepsis were significantly higher than in the controls. In patients with sepsis, non-survivors had higher ET-1 levels than survivors on day 1 and 7, and patients with shock also had higher ET-1 levels than normotensive patients on admission. The ET-1 levels were significantly correlated with the creatinine levels on day 1, 7, and 14. The IL-8 levels showed a significant correlation with the ET-1 levels on day 14. Conclusion : ET-1 was found to be closely related with the clinical outcome, shock, and renal failure, and showed a correlation with IL-8. These mediators can be considered not only to play pathophysiologic roles but also as useful parameters in the clinical assessment of sepsis.

• Korean Journal of Food Science and Technology
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• v.50 no.3
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• pp.349-355
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• 2018

Ginsenoside Rg5, one of the protopanaxadiol ginsenosides of wood-cultivated ginseng, has been implicated in various diseases, such as diabetes, cancer, and hypertension; however, its angiogenic activity and molecular mechanisms have not yet been elucidated. Here, we found that wood-cultivated ginseng extract and ginsenoside Rg5 increase in vitro proliferation, migration, and tube-like structure formation, which are typical phenomena associated with angiogenesis, in cultured human umbilical vein endothelial cells (HUVECs). Moreover, Ginsenoside Rg5 stimulated the phosphorylation of Akt, endothelial nitric oxide (NO) synthase (eNOS), and extracellular-regulated kinase (ERK)1/2, which are well-known signal mediators of the angiogenic pathway. Furthermore, Ginsenoside Rg5 did not accelerate the activation of ICAM-1 and VCAM-1 which are inflammatory response mediators. These results suggest that wood-cultivated ginseng extract and ginsenoside Rg5 stimulated in vitro angiogenesis by activating the Akt/eNOS- and ERK1/2-dependent signal pathways without inducing vascular inflammation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.501-509
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• 2016

The present study investigated the anti-atopic effects of mixed extracts from date plum, persimmon, and mulberry leaves (DPME) on atopic dermatitis (AD)-like skin lesions in hairless mice. The in vivo results demonstrated that DPME treatment significantly reduced the dermatitis clinical score and epidermal thickness in AD-like skin lesions. Histological analyses showed that DPME treatment strongly inhibited dermal infiltration of inflammatory cells and activity of mast cells in AD-like skin lesions. DPME treatment inhibited production of serum IgE and interluekin (IL)-4 in hairless mice with AD. Moreover, DPME treatment significantly suppressed production of tumor necrosis factor $(TNF)-{\alpha}$ and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. In addition, DPME treatment reduced production of pro-inflammatory mediators (nitric oxide, prostaglandin E2, $TNF-{\alpha}$, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Therefore, the results of this study indicate that the anti-atopic and anti-inflammatory effects of DPME may be involved in the regulation of inflammatory responses, suggesting that DPME may be used as an anti-atopic dermatitis material and natural anti-inflammatory ingredient.

• Microbiology and Biotechnology Letters
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• v.43 no.2
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• pp.112-119
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• 2015

The anti-inflammatory effect of Sargassum coreanum ethanolic extract (SCEE) was investigated using lipopolysaccharide (LPS)-induced inflammatory responses in this study. It was shown that there was no cytotoxicity in the viability of macrophages treated with SCEE when compared to the control. The production of NO was considerably suppressed by SCEE, approximately up to 50% at 100 μg/ml. This significantly decreased levels of IL-6, TNF-α, and IL-1β. In addition, the expression of iNOS, COX-2, NF-κB was suppressed by SCEE treatment. In in vivo testing, the croton oil-induced mouse ear edema was attenuated by SCEE and there were no mortalities in mice administered with 5000 mg/kg body weight of SCEE over a 2 week observation period. From these results, SCEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SCEE could be a potential agent for anti-inflammatory therapies.