• Tuberculosis and Respiratory Diseases
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• v.54 no.2
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• pp.199-209
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• 2003

Background : Unexplained weight loss, which commonly occurs in patients with chronic obstructive pulmonary disease(COPD), is important because weight loss is an independent risk factor of mortality and morbidity in these patients. Leptin is known to play an important role in regulating body weight. In addition, the tumor necrosis factor($TNF-{\alpha}$) might also play a potential role in the weight loss experienced in chronic wasting disease. The aim of this study was to determine the influence of plasma leptin and the circulating $TNF-{\alpha}$ system to the difference in the body compositions in patients with COPD. Methods : Spirometry, body composition analysis and the plasma concentrations of leptin, $TNF-{\alpha}$ and a soluble TNF receptor (STNF-R55, -R75) were measured in 31 patients with chronic bronchitis and 10 patients with emphysema. The COPD subtype was classified by the transfer coefficient of carbon monoxide, DLco/VA. Results : The circulating levels of leptin were significantly lower in those patients with emphysema($108.5{\pm}39.37pg/ml$) than those with chronic bronchitis($180.9{\pm}57.7pg/ml$). The circulating levels of sTNF-R55 were significantly higher in the emphysema patients($920.4{\pm}116.4pg/ml$) than in those with chronic bronchitis($803.2{\pm}80.8pg/ml$). There was no relationship between the circulating leptin levels and the activated TNF system in patients with chronic bronchitis and emphysema. However, the circulating leptin levels correlated well with the BMI and fat mass in both patient groups. Conclusion : These results suggest that the weight loss noted in emphysema patients may be associated with the activation of the $TNF-{\alpha}$ system rather than the plasma leptin level.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.308-322
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• 1996

Background : Neutrophils are considered to play critical roles in the development of acute respiratory distress syndrome. Histamine, which is distributed abundantly in lung tissue, increases the rolling of neutrophills via increase of P-selectin expression on the surface of endothelial cells and is known to have some interrelationships with IL-1, IL-8 and TNF-$\alpha$. We studied to investigate the effect of the histamine on the acute lung injury of the rats induced by intratracheal insufflation of TNF-$\alpha$ which has less potency to cause lung injury compared to IL-1 in rats. Methods : We intratracheally instilled saline or TNF(R&D, 500ng), IL-1(R&D, 50ng)or histamine of varius dose(1.1, 11 and $55\;{\mu}g/kg$) with and without TNF separately in Sprague-Dawley rats weighing 270-370 grams. We also intratracheally treated IL-1(50ng) along with histamine($55\;{\mu}g/kg$). In cases, there were synergistic effects induced by histamine on the parameters of TNF-induced acute lung injury, antihistamines(Sigma, mepyramine as a $H_1$ receptor blockade and ranitidine as a $H_2$ receptor blockade, 10 mg/kg in each)were co-administered intravenously to the rats treated TNF along with histamine($1.1\;{\mu}g/kg$) intratraeheally. Then after 5 h we measured lung lavage neutrophil numbers, lavage cytokine-induced neutrophil chemoattractants(CINC), lung myeloperoxidase activity(MPO) and lung leak. We also intratracheally insufflated TNF with/without histamine($11\;{\mu}g/kg$), then after 24 h measured lung leak in rats. Statistical analyses were done by Kruskal-Wallis nonparametric ANOVA test with Dunn's multiple comparison test or by Mann-Whitney U test. Results : We found that rats given TNF, histamine alone(11 and $55\;{\mu}g/kg$), and TNF with histamine(l.1, 11, and $55\;{\mu}g/kg$) intratracheally had increased (p<0.05) lung MPO activity compared with saline-treated control rats. TNF with histamine $11\;{\mu}g/kg$ had increased MPO activity (P=0.0251) compared with TNF-treated rats. TNF and TNF with histamine(1.1, 11, and $55\;{\mu}g/kg$) intratracheally had all increased (p<0.05) lung leak, lavage neutophil numbers and lavage CINC activities compared with saline. TNF with histamine $1.1\;{\mu}g/kg$ had increased (p=0.0367) lavage neutrophil numbers compared with TNF treated rats. But there were no additive effect of histamine with TNF compared with TNF alone in acute lung leak on 5 h and 24 h in rats. Treatment of rats with the $H_1$ and $H_2$ antagonists resulted in inhibitions of lavage neutrophil accumulations and lavage CINC activity elevations elicited by co-treated histamine in TNF-induced acute lung injury intratracheally in rats. We also found that rats given IL-1 along with histamine intratracheally did not have increase in lung leak compared with IL-1 treated rats. Conclusion : Histamine administered intratracheally did not have synergistic effects on TNF-induced acute lung leak inspite of additive effects on increase in MPO activity and lavage neutrophil numbers in rats. These observations suggest that instilling histamine intratracheally would not play synergistic roles in neutrophil-mediated acute lung injury in rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1439-1449
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• 2015

Prunus persica Flos (PPF) were investigated for their antioxidant and anti-inflammatory activities to find a natural functional food resource preventing degenerative diseases associated with excessive oxidative stress and chronic inflammation. PPF was extracted using ethanol (EtOH) and then sequentially fractioned by hexane (Hx), dichloromethane (DM), ethyl acetate (EA), n-butanol (BtOH), and water (DW). Contents of total phenolics and flavonoids, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities were measured. Anti-inflammatory effects in terms of nitric oxide (NO), prostaglandin (PG) E2, and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ production were also measured using LPS-treated RAW 264.7 macrophages. EtOH extract showed relatively high antioxidant activity with high total phenolic (78.1 mg tannic acid/g) and flavonoid contents (55.3 mg rutin/g). EA fraction contained the highest total phenolic and flavonoid contents (394.6 mg tannic acid/g, 253.7 mg rutin/g), followed by BtOH (128.3 mg tannic acid/g, 93.1 mg rutin/g). EA and BtOH fractions and EtOH extract showed higher DPPH radical and ABTS radical scavenging activities than the others (P<0.05). In LPS-treated RAW 264.7 macrophages, EtOH extract ($200{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, and TNF-${\alpha}$ production levels to 38.5%, 32.3%, and 48.9% of the control, respectively, as well as reduced iNOS and COX-2 protein expression. DM fraction ($50{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 43.5%, 13.3%, 38.7%, and 41.3% of the control, respectively, and EA fraction ($50{\mu}g/mL$) showed significantly reduced NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 44.8%, 22.4%, 45.7%, and 62.0% of the control, respectively. Taken together, EtOH extract of PPF showed potent antioxidant and anti-inflammatory activities, and EA and BtOH fractions showed comparatively stronger antioxidant activities while DM and EA fractions showed stronger anti-inflammatory activities. It can be concluded that EtOH extract of PPF and its fractions are good candidates as natural resources for the development of anti-oxidative and anti-inflammatory functional food products.

• Korean Journal of Veterinary Research
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• v.55 no.2
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• pp.81-88
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• 2015

This study was conducted to isolate lactic acid bacteria (LAB) from dog intestine and identify potential probiotic strains for canine use. One hundred and one LAB were isolated from feces of 20 healthy dogs. Acid, bile, and heat resistance along with adherence to Caco-2 cells and antimicrobial activity against pathogens were examined. To analyze immunomodulative effects, the production of nitric oxide (NO), TNF-${\alpha}$, and IL-$1{\beta}$ was measured using RAW 264.7 macrophages. Additionally, RAW BLUE cells were used to evaluate nuclear factor-${\kappa}B$ (NF-${\kappa}B$) generation. Ultimately, three strains were selected as canine probiotics and identified as Lactobacillus reuteri L10, Enterococcus faecium S33, and Bifidobacterium longum B3 by 16S rRNA sequence analysis. The L10 and S33 strains showed tolerance to pH 2.5 for 2 h, 1.0% Oxgall for 2 h, and $60^{\circ}C$ for 5 min. These strains also had strong antimicrobial activity against Escherichia coli KCTC 1682, Salmonella Enteritidis KCCM 12021, Staphylococcus aureus KCTC 1621, and Listeria monocytogenes KCTC 3569. All three strains exerted better immunomodulatory effects than Lactobacillus rhamnosus GG (LGG), a well-known commercial immunomodulatory strain, based on NO, NF-${\kappa}B$, IL-$1{\beta}$, and TNF-${\alpha}$ production. These results suggested that the three selected strains could serve as canine probiotics.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.21-30
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• 2003

Background : Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method : MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, $TNF{\alpha}$ was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal $TNF{\alpha}$ antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results : LPS alone did not increase significantly MUC5AC production. LPS with $TNF{\alpha}$ induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently $TNF{\alpha}$ secretion, which was inhibited by mastoparan. LPS with $TNF{\alpha}$-induced MUC5AC production was inhibited by neutralizing polyclonal $TNF{\alpha}$ antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion : In LPS-induced MUC5AC synthesis, LPS causes $TNF{\alpha}$ secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.360-378
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• 1997

Background : Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And there is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALI through a time course of changes in the concentration of protein, $TNF{\alpha}$ and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. Method : The experimental animals, healthy male Sprague-Dawley, weighted $200{\pm}50g$, were divided into control- and ALI- group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. $TNF{\alpha}$ and IL-6 cone. in BALF were measured by a bioassay. Results : The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p < 0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p < 0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p < 0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r = 0.97, p < 0.001) appeared to be more meaningful than that of monocyte(r = 0.61, p < 0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte : r = 0.55, p < 0.005 vs. r = 0.64, p < 0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this study, there was no relationship between IL-6 and $TNF{\alpha}$ cone., and $TNF{\alpha}$ but not IL-6 was correlated with TC(r = 0.61, p < 0.05) and monocyte(r = 0.67, p < 0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than $TNF{\alpha}$ cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p < 0.001 vs. NC). Alveolar wall-thickness was increased from 6 to 24h(p < 0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p < 0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. Conclusion : We concluded that although the role of PMN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to $TNF{\alpha}$, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.

• 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.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.41 no.1
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• pp.45-55
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• 2015

Ultraviolet B (UVB) irradiation induces both production of reactive oxygen species (ROS) and glucocorticoids (GCs)-mediated stress responses such as an increase of $11{\beta}$-hydroxysteroid dehydrogenase type 1 ($11{\beta}$-HSD1) activity in skin. In addition, ROS-induced inflammatory mediators and proinflammatory cytokines trigger skin inflammation. In this study, as $11{\beta}$-HSD1 inhibitor recovered a decrease of catalase expression, we investigated whether Trapa japonica (TJ) extract and its fractions could inhibit $11{\beta}$-HSD1/ROS-induced skin inflammation in HaCaT keratinocytes. TJ extract and its fractions inhibited expressions of $11{\beta}$-HSD1 as well as the increase of ROS in UVB-exposed HaCaT keratinocytes. Moreover, proinflammatory cytokines such as interleukin (IL)- ${\alpha}$, - ${\beta}$ and tumor necrosis factor (TNF)-${\alpha}$, and cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) as inflammatory mediators were also inhibited in both mRNA and protein levels. Finally, prostaglandin $E_2$ ($PGE_2$) produced by COX-2 was inhibited effectively by TJ extract and its fractions. Taken together, these results suggest that TJ extract could be a potential anti-inflammatory ingredient to inhibit UVB-induced inflammation in skin.

• Journal of Animal Environmental Science
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• v.18 no.sup
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• pp.55-64
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• 2012

We investigated the effect of the clay mineral fortified with complex trace elements by specific fermentation microbes on growth performance and a quality of pork in this study. For the declared experimental animal, 80 heads of crossbred with Large White and Yorkshire were randomly splitted into a control group and a test group. Each group were assigned with 4 replicates and 10 heads of each replicate. When 0.3% of the fermentation product of the clay mineral (FCM) was added into feed stuff and fed for 9 weeks of experimental feeding period, the results of the feed intake, weight gains, pH of carcass, lightness of meat color, and brightness of the muscle semimembranosus were similar to those of the control group. However, dressing percentage, reddishness of carcass, and water holding capacity were improved, respectively, as much as 2.7%, 12%, and 10%, and reduced by 6% in cooking loss. In order to investigate the immune modulatory effect of fermented clay mineral, pheripheral blood mononuclear cells (PBMC) were isolated and Immune modulatory parameters were measured. The proliferation activity of PBMC from pigs fed the fermented clay mineral were significantly increased compared to control group pigs, and also those results were more clearly observed as activated with lipopolysaccharide and concanavaline A. The secretion of TNF-${\alpha}$ of the FCM group pigs showed an increasing tendency. Therefore it was suggested that the feeding of FCM which was high in cation metathesis and the value of infrared ray, activated the immune responses, and thus the production of the environment-friendly high quality pork without the use of antibiotics would be possible.

• 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.