• Title/Summary/Keyword: Interleukin 10

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Promotion effects of steam-dried Betula platyphylla extract on hair regrowth (자작나무 증포 추출물의 발모 촉진 효과)

  • Ahn, Jeong Won;Jang, Su Kil;Jo, Bo Ram;Kim, Hyun Soo;Jeoung, Eui Young;Hillary, Kithenya;Yoo, Yeong Min;Joo, Seong Soo
    • Korean Journal of Food Science and Technology
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    • v.54 no.1
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    • pp.43-51
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    • 2022
  • Regulation of the hair follicle cycle in association with dermal papilla cells is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether steam-dried Betula platyphylla extracts (BPE) promote hair growth by upregulating in vitro and in vivo responses of dermal papilla cells. The data showed that BPE3 contained high amounts of phenolic compounds with higher antioxidant effects and increased hair growth-related genes, including fibroblast growth factor7 and Wnt7b, in dermal papilla cells. Notably, BPE3 effectively enhanced the formation of hair follicles by increasing FGF7, Wnt7b, and vascular endothelial growth factor in C57BL/6N dorsal skins. Additionally, BPE3 significantly decreased the expression of inflammatory repertoires, inducible nitric oxide synthase, interleukin-6, and cyclooxygenase 2. Several small molecules, such as betulin and unsaturated fatty acids, support the pharmacological activity of BPE3. In conclusion, BPE3 effectively promoted hair growth by activating dermal papilla cells and enhancing hair follicle cycles by attenuating the inflammatory environment in the scalp.

Anti-inflammatory Effects of Rumohra adiantiformis Extracts Fermented with Bovista plumbea Mycelium in LPS-stimulated RAW 264.7 Cells (LPS로 자극된 RAW 264.7 세포에서 찹쌀떡버섯 균사체로 생물전환된 루모라고사리 추출물의 항염증 효과)

  • Ji-Hye Hong;Eun-Seo Jang;Myung-Chul Gil;Gye Won Lee;Young Ho Cho
    • Journal of Life Science
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    • v.33 no.6
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    • pp.471-480
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    • 2023
  • This study was designed to evaluate the anti-inflammatory effects of Rumohra adiantiformis extracts fermented with Bovista plumbea mycelium (B-RAE) in LPS-stimulated RAW 264.7 cells. The total polyphenol and total flavonoid content of B-RAE were 379.26±7.77 mg/g and 50.85±3.08 mg/g, respectively. The results of measuring the antioxidant activity of B-RAE showed that it scavenges 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and superoxide anion radical in a dose-dependent manner. B-RAE inhibited nitric oxide (NO) production in a dose-dependent manner without affecting cell viability. The gene expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-lβ (IL-1β), and IL-6 was measured using real time quantitative reverse transcription PCR (qRT-PCR). We found that, compared to the LPS-treated group, B-RAE significantly reduced the mRNA levels of the pro-inflammatory cytokines in a concentration-dependent manner. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the phosphorylation of transcription factors such as nuclear factor-κB (NF-κB), and the mitogen-activated protein kinase (MAPK) signaling pathway proteins were assessed using Western blot analysis. We found that B-RAE significantly suppressed the expression of iNOS and COX-2, but their expression was increased by LPS treatment. In addition, the phosphorylation of NF-κB and IκB, which was increased by LPS treatment, was reduced with B-RAE treatment. The effect of B-RAE on the phosphorylation of the MAPK signaling pathway proteins was measured, and the phosphorylation of extracellular signal-regulated kinase (ERK) and the p38 MAPK proteins decreased in a dose-dependent manner, while the phosphorylation of c-Jun N-terminal kinase (JNK) increased. These anti-inflammatory effects of B-RAE may thus have been achieved through the high antioxidant activity, the inhibition of NO production through the suppression of iNOS and COX-2 expression, the inhibition of the NF-κB pathway, and the suppression of pro-inflammatory cytokine expression.

Anti-inflammatory Effects, Skin Wound Healing, and Stability of Bluish-purple Color Extracted from Platycodon grandiflorus (Jacq.) A.DC. Flower Extract (도라지꽃 추출물의 항염증, 피부재생 효과 및 색소 안정성 연구)

  • Jin-A Ko;Jiwon Han;Bomi Nam;Beom seok Lee;Jiyoung Hwang
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.49 no.4
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    • pp.313-321
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    • 2023
  • Platycodon grandiflorus (P. grandiflorus) flower is a perennial plant belonging to the family Campanulaceae and has many excellent pharmacological effects, so it has been used as a medicinal ingredient since ancient times. In addition, anthocyanin is a purple or blue natural pigment contained in plant flowers and fruits, and is known as a powerful antioxidant. The purpose of this study was to confirm the dermatological functionality of P. grandiflorus flower extract and the value of the bluish anthocyanin contained in flowers as a cosmetic material as a natural pigment. Firstly, 50% ethanol and 80% ethanol were added to the P. grandiflorus flower and extracted under reflux for 4 h at 25, 60, and 80 ℃, and the pH of each treatment group was similar. Based on the anthocyanin content and chromaticity (E*ab), 50% ethanol 60 ℃ extraction conditions showing the color development most similar to the natural color of the P. grandifloras flower were selected, and a sample was prepared by concentrating and lyophilizing. The analysis results showed that the total phenol, total flavonoid, and total anthocyanin contents were in the ranges of 23 ㎍/mL, 16 ㎍/mL, and 0.17 ㎍/mL, respectively. The P. grandiflorus flower extract suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6) in lipopolysaccharide (LPS) induced RAW264.7 cells. Furthermore, the P. grandiflorus flower extract showed wound healing effects through the promotion of skin cell migration in TNF-α stimulated human keratinocytes. The stability of anthocyanin and extract color was studied during a storage period of 50 days at various temperatures (4 ℃, 25 ℃, and 45 ℃). Color values (L, a, and b) of the P. grandiflorus flower extract changed over 50 days, whereas the bluish-purple color of the extract was stabilized using 5% maltodextrin. These results suggest that P. grandiflorus flower extract may be useful as a natural cosmetic pigment.

In vitro Antioxidant and Anti-Inflammatory Activities of Ethanol Extract and Sequential Fractions of Flowers of Prunus persica in LPS-Stimulated RAW 264.7 Macrophages (복숭아꽃 에탄올 추출물과 분획물의 in vitro 항산화 효과 및 RAW 264.7 대식세포에서의 항염증 효과)

  • Kwak, Chung Shil;Choi, Hye-In
    • 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.

Effect of Boswellia serrata Extracts on Degenerative Osteoarthritis in vitro and in vivo Models (보스웰리아 추출물의 골관절염 억제 효과 연구)

  • Nam, Da-Eun;Kim, Ok Kyung;Shim, Tae Jin;Kim, Ji Hoon;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.5
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    • pp.631-640
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    • 2014
  • The inhibitory effects of Boswellia serrata (BW) extracts on degenerative osteoarthritis were investigated in primary-cultured rat cartilage cells and a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. To identify the protective effects of BW extract against $H_2O_2$ ($800{\mu}M$, 2 hr) in vitro, cell survival was measured by MTT assay. Cell survival after $H_2O_2$ treatment was elevated by BW extract at a concentration of $20{\mu}g/mL$. In addition, BW extract treatment significantly reduced and normalized the productions of pro-inflammatory factors, nuclear transcription factor ${\kappa}B$, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interleukin-6 at a concentration of $20{\mu}g/mL$. Treatment of chondrocytes with BW extract significantly reduced 5-lipoxygenase activity and production of prostaglandin E2, especially at a concentration of $10{\sim}20{\mu}g/mL$. For the in vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats. Consumption of a diet containing BW extract (100 and 200 mg/kg) for 35 days significantly inhibited the development and severity of osteoarthritis in rats. To determine the genetic expression of arthritic factors in articular cartilage, real-time PCR was applied to measure matrix metalloproteinases (MMP-3, MMP-9, and MMP-13), collagen type I, collagen type II, and aggrecan, and BW extract had protective effects at a concentration of 200 mg/kg. In conclusion, BW extract was able to inhibit articular cartilage degeneration by preventing extracellular matrix degradation and chondrocyte injury. One can consider that BW extract may be a potential therapeutic treatment for degenerative osteoarthritis.

Soluble IL-2R, IFN-$\gamma$ and Neopterin as Immunologic Markers in Patients with Tuberculosis (결핵 환자에서 면역학적 지표로서의 sIL-2R, IFN-$\gamma$, Neopterin에 관한 연구)

  • Ryu, Yon-Ju;Ryu, Kum-Hei;Kim, Su-Hyun;Lee, Jong-Soo;Cheon, Seon-Hee;Seoh, Ju-Young
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.294-308
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    • 2002
  • Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

Effects of Ojeoksangamibang on the Lipid Metabolism, Anti-oxidation and Concentration of Proinflammatory Cytokines in Rat Fed High Fat Diet (오적산가미방(五積散加味方)이 고지방식이 유도 비만쥐의 지질대사, 항산화계 및 전염증성 cytokine 생산에 미치는 영향)

  • Kong, In-Pyo;Park, Won-Hyung;Cha, Yun-Yeop
    • Journal of Korean Medicine Rehabilitation
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    • v.21 no.4
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    • pp.23-40
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    • 2011
  • Objectives: This study was designed to examine the effects of extracts of Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) on the lipid lowering, anti-oxidation and concentration of proinflammatory cytokines and was investigated on hyperlipidemic rats. Methods: Male rats weighing $182.39{\pm}4.71g$ were fed high fat diet for 8 weeks and 36 rats(above 400 g) were divided into 4 groups. Each of 9 rats was divided a control group and experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1 time/1 day) for 4 weeks. And we fed each experimental group of rats basal diet and administered an extract of Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) extracts(100 mg/kg, 200mg/kg, 300 mg/kg, 300 mg/kg, 1 time/1 day) for 4 weeks. At the end of the experiment, the rats were sacrificed to determine their chemical composition. We measured lipid of plasma and liver, concentration of proinflmmatory cytokines, anti-oxidative activity and $TNF-{\alpha}$, Apo-B, Apo-E and leptin gene expression. Results: 1. Concentration of plasma free fatty(FFA) showed no significant difference in all the treatment groups. Concentration of plasma triglyceride(TG) showed a significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. 2. Concentration of plasma total cholesterol showed a significant decrement in the 200 and 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. Concentration of plasma low density lipoprotein(LDL)-cholesterol showed a Significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. Concentration of plasma high density lipoprotein(HDL)-cholesterol showed a significant increment in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group. 3. Concentration of liver total cholesterol showed a tendence to decrease in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups. Concentration of liver TG showed a significant decrement in all Ojeoksangamibang groups than that of control group. 4. Concentration of plasma and liver thiobarbituric acid reactive substance(TBARS) showed a tendence to decrease in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups. 5. The values of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and catalase(CAT) activity showed a significant increment in all Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. 6. The values of plasma aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activity showed no significant different in all treatment group. 7. Concentration of plasma $interleukin(IL)-1{beta}$ showed no significant difference in all the treatment groups. Concentration of plasma IL-6 showed a significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group than that of control group. Concentration of plasma tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ a siginifant decrement in the 200 and 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group than that of control group. However the concentration of plasma IL-10 in the 300 mg/kg Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a significant increment than that of control group. 9. In the analysis of reverse transcription-polymerase chain reaction(RT-PCR), gene expression of $TNF-{\alpha}$, Apo-B and Apo-E in the Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a lower expression than that of control group. However the gene expression of leptin showed no difference in the treatment groups. 10. The ratio of $TNF-{\alpha}$, Apo-B, and Apo-E per ${\beta}-actin$ expression in the Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a significant decrement than that of control group. However The ratio of leptin expression per ${\beta}-actin$ expression showed no significant difference among all the treatment groups. Conclusions: According to above results, in lowering lipid effect, anti-oxidation and control of pro-inflammatory cytokines production, Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) gives effect.

Anti-inflammatory Effects of Pentoxifylline and Neutrophil Elastase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury In Vitro (In Vitro 내독소 유도성 급성 폐손상에서 Pentoxifylline과 Neutrophil Elastase Inhibitor의 항염효과)

  • Kim, Young-Kyoon;Kim, Seung-Joon;Park, Yong-Keun;Kim, Seok-Chan;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak;Kim, Sang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.691-702
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    • 2000
  • Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

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The Value of Interleukin-12 as an Activity Marker of Pulmonary Sarcoidosis (폐유육종증의 활동성 지표로서 IL-12의 효용성에 관한 연구)

  • Kim, Tae-Hyung;Jeon, Yong-Gam;Shim, Tae-Sun;Lim, Chae-Man;Koh, Yun-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.2
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    • pp.215-228
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    • 1999
  • Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

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Efficacy of Interferon-Gamma Treatment in Bronchial Asthma (기관지천식에서 Interferon-Gamma 치료의 효과)

  • Kim, Kwan-Hyoung;Kim, Seok-Chan;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Chi-Hong;Moon, Hwa-Sik;Song, Jung-Sup;Park, Sung-Hak;Lee, Choong-Eon;Byun, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.822-835
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    • 1997
  • Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

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