• Journal of Microbiology and Biotechnology
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• v.19 no.4
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• pp.424-430
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• 2009

IL-10 is an important anti-inflammatory cytokine that can inhibit the production of many pro-inflammatory cytokines. Both human and animal studies have shown that pro-inflammatory cytokines play an important role in pneumonia and other inflammatory lung diseases. In the present study, IL-10 knockout(KO) and wild-type mice were infected with Corynebacterium kutscheri to determine whether the severity of pathogenesis and whether protective immunity could be altered in the absence of IL-10. The survival rate was significantly lower in IL-10 KO mice than wild-type mice. The number of neutrophils in bronchoalveolar lavage fluid and blood were found to be higher in IL-10 KO mice than wild-type mice. IL-10 KO mice showed greater neutrophil infiltration, excessive inflammation, and weight-loss compared with wild-type mice. Furthermore, upregulation of IFN-$\gamma$ in bronchoalveolar lavage fluid, and upregulation of MIP-$1{\alpha}$ and IP-10 mRNA in the lungs of IL-10 KO mice compared with wild-type mice after C. kutscheri infection were observed. These results suggest that IL-10 plays an important role in the anti-inflammatory properties against C. kutscheri infection, and that lack of IL-10 leads to a more severe pulmonary inflammatory response. This increased susceptibility to C. kutscheri pneumonia is at least in part caused by IL-10 deficiency and severe recruitment of neutrophils.

• YAKHAK HOEJI
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• v.48 no.2
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• pp.159-164
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• 2004

Primary pro-inflammatory cytokines are a trio: tumor necrosis- $\alpha$ (TNF-$\alpha$), interleukine-$\beta$ (IL-$\beta$), and interleukine-6 (IL-6). These cytokines initiate and regulate the acute-phase inflammatory response during infection, trauma, or stress and appear to play an important role in the immune process. Nitric oxide (NO) is a multi-functional mediator, which plays an important role in regulating various biological functions in vivo. NO production by inducible nitric oxide synthase (iNOS) in macrophages is essential for the defense mechanisms against microorganisms and tumor cells. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammatory and auto-immune disease. Solvent fractions of sage ( Salvia officinalis L.), which is cultivated in Jeju-Do, was assayed for their effects on TNF-$\alpha$ and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Hexane and ethylacetate (EtOAc) fraction of sage inhibited the protein and mRNA expression of TNF-$\alpha$ and IL-6 in LPS stimulated RAW 264.7 cells at the concentration of 100 $\mu\textrm{g}$/$m\ell$. Also, incubation of RAW 264.7 cells with the fraction of hexane or EtOAc (50 $\mu\textrm{g}$/$m\ell$) inhibited the LPS induced nitrite accumulation and the LPS/IFN-${\gamma}$ induced iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. Above results suggest that extract of sage may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6), iNOS and NO.

• Journal of Chest Surgery
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• v.33 no.8
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• pp.648-654
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• 2000

Background: Cardiopulmonary bypass during open heart surgery causes systemic inflammatory respose. IL-10 is an anti-inflammatory cytokine that inhibits inflammatory process and protects organ function by down regulation of pro-inflammatory cytokine release and maintenance of blood level balance with pro-inflammatory cytokines. Mateial and Method: Plasma IL-10 levels were measured and analyzed in 22 patients who underwent open heart surgery (11 cases of coronary artery bypass graft, 11 cases of valve replacement) under cardiopulmonary bypass since 1988 January to July at Department of Thoracic and Czardiovascular surgery, Yeungnam University Hospital. 1g of methylprednisolone was administrated to thirteen patients randomly. Blood samp.es were taken and collected at the time of induction of anesthesia, 10 min before cardiopulmonary bypass, 10 min after starting of CPB, 10 min aftr aortic cross clamping, 10 min after ACC release, and 10 min, 2 hours, and `5 hours after CPB respectively. The plasma levels of IL-10 were determined by enzyme-linked immunosorbent assays(ELISA). Wilcoxon-Raule Sum test was used for statistical analysis. Result: In all 22 patients, cardiopulmonary bypass time was used for statistical analysis. Result: In all 22 patients, cardiopulmonary bypass time was 171$\pm$41.4 min and aortic cross clamp time was 118$\pm$36.5 min. Peak IL-10 level was achieved at 10 min after ACC(361.0$\pm$52.81pg/ml) and was decreased sharply at 2 hours after CPB. Peak IL-10 level was correlated positively with aortic cross clamp time(p=0.011); however, it did not correlated with bypass time(p=0.181). In valve replacement group, mean IL-10 level at peak point was 567.89$\pm$107.69 pg/ml and was significantly higher than that of coronary artery bypass group(205.67$\pm$192.70 pg/ml)(p<0.001). ACC time in valve replacement group was significantly longer than that of coronary artery bypass group(p<0.01), however, bypass time was not(p=0.212). Thirteen patients with steroid pretreatment before starting of CPB showed relatively higher plasma IL-10 level than in control group, however, no statistical significance was noted(p=0.19). Conclusion: plasma level of IL-10 was increased in association with cardiopulmonary bypass and revealed peak at 10 min after ACC release. IL-10 level was correlated positively with ACC time. Therefore, systemic inflammatory respeonse in association with cardiopulmonary bypass could be decreased by reducing ACC time during cardiac surgery.

• Food Science and Preservation
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• v.23 no.7
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• pp.1026-1032
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• 2016

Citrus platymamma hort. ex Tanaka is widely used in traditional Korean medicine because of its medicinal benefits including an anti-inflammatory effect. This study aimed to evaluate changes in the flavonoid content and anti-inflammatory activities of C. platymamma during its harvest period. Fruit peel samples were obtained between September 2015 and February 2016. The results indicate that C. platymamma peel extract (CPE) was an effective inhibitor of lipopolysaccharide (LPS)-induced NO production in RAW264.7 cells. The inhibitory effects of CPE at $100{\mu}g/mL$ concentration included dose-dependent decreases in the expression of iNOS and COX-2 proteins. In addition, CPE decreased the expression of pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. The highest anti-inflammatory activity and flavonoid content were observed in CPE of C. platymamma peel harvested during the immature fruit period in September. Further, to assess the suitability of CPE for cosmetic use, we performed MTT assays using HaCaT keratinocytes and observed that CPE did not exhibit any cytotoxicity. To test the potential application of CPE as a cosmetic material, we also performed primary skin irritation tests on normal skin of 30 volunteers and no adverse reactions were observed. The results of this study indicate that CPE may be considered as an anti-inflammatory candidate for inclusion in cosmetic materials.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.117-124
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• 2017

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interferon (IFN)-${\gamma}$, and interleukin (IL)-$1{\beta}$] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-${\alpha}$; 5 ng/ml, IFN-${\gamma}$; 5 ng/ml, and IL-$1{\beta}$; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.26 no.2
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• pp.45-57
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• 2013

Objectives : Daucus carota sativa has been frequently used as food supplements in many of the Asian countries, and a nutritional medical drug in traditional medicine. This research investigated the effects of Daucus carota sativa extract (DCE) on acute phases of inflammation in Raw 264.7 cells treated with lipopolysaccharide (LPS) in terms of the inhibition of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines production. Methods : NO, $PGE_2$, tumor necrosis factor (TNF)-${\alpha}$, interleukin-$1{\beta}$ and interleukin-6 contents were assayed by ELISA, and expressions of inflammation-related proteins such as inducible NO synthase (iNOS) were determined by immunoblot analyses. Results : DCE treatment attenuated the LPS ability to increase the productions of NO and $PGE_2$ as well as the protein level of iNOS in a concentration-dependent manner. Consistently, treatment of the cells with DCE suppressed the production of TNF-${\alpha}$, interleukin-$1{\beta}$ and interleukin-6. DCE also caused decreases of inhibitor of ${\kappa}B{\alpha}$ phosphorylation induced by LPS in the cells, which means DCE inhibition of NF-${\kappa}B$ activity. Furthermore, DCE blocked LPS-induced phosphorylation of p38 and SAPK/JNK. Conclusion : This study showing here may be of help to understand the action mechanism of DCE, and provide the information for the medical use of Daucus carota sativa for the inflammatory disease.

• Korean Journal of Food Science and Technology
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• v.52 no.5
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• pp.482-486
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• 2020

Cases of inflammatory bowel diseases including ulcerative colitis are increasing in Korea and development of non-steroidal anti-inflammatory drugs (NSAIDs) are widely investigated. Natural products with anti-inflammatory properties are rising as safe candidates for NSAIDs. The extract of turmeric or puffed turmeric mixed with herbal extract (goji berry, liquorice, lycium root, and dong quai) was treated to acute colitis mice by oral gavage. The symptoms of colitis, i.e., body weight loss, fecal score, and shortened colon length, were significantly attenuated by puffed turmeric extract with the herbal extract. Non-puffed turmeric extract with herbal extract, however, exhibited a very marginal recovery. Tissue culture supernatant of colons further revealed that both puffed turmeric and non-puffed turmeric extracts with herbal extract suppressed pro-inflammatory cytokine production at a comparable level. These results indicate that puffing is a simple and promising process of turmeric for enhancement of anti-inflammatory properties.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.97-101
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• 2011

Cirsium japonicum var. ussuriense is known to have a variety of biological activities, including anti-inflammatory, analgesic activity and antipyretic activity. In this study we investigated the role of polyacetylene compound, 1-Heptadecene-11, 13-diyne-8, 9, 10-triol (PA) from the root of Cirsium japonicum var. ussuriense as an immune-modulator. PA was evaluated as inhibitors of some macrophage functions involved in the inflammatory process. We tested the effect of PA on the production of pro-inflammatory cytokines, interleukin-1beta (IL-$1{\beta}$) and tumor necrosis factor-alpha (TNF-$\alpha$), and nitric oxide (NO) in murine macrophage cell line, RAW264.7. There was no effect on cytokine production of macrophages by PA itself. However, PA inhibited lipopolysaccharide (LPS)-induced IL-$1{\beta}$ and TNF-$\alpha$ production by macrophages at a dose dependent manner. PA also suppressed the NO production of macrophages by LPS. LPS-induced NF-${\kappa}B$ activity was decreased by treatment of PA. Therefore, these results suggest that PA has anti-inflammatory effect by inhibiting the NF-${\kappa}B$ activation.

• IMMUNE NETWORK
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• v.10 no.5
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• pp.145-152
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• 2010

Background: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). Methods: The anti-inflammatory effects of IFE against nitric oxide (NO), $PGE_2$, TNF-${\alpha}$, and IL-6 release, as well as NF-${\kappa}B$ and MAP kinase activation were evaluated in RAW 264.7 cells. Results: IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-${\alpha}$ and IL-6. Furthermore, IFE inhibited the NF-${\kappa}B$ activation induced by LPS, which was associated with the abrogation of $I{\kappa}B-{\alpha}$ degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. Conclusion: These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-${\kappa}B$ activation via suppression of $I{\kappa}B{\alpha}$ and MAP kinase phosphorylation in macrophages.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.110-123
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• 2005

Objectives : This study was performed to examine the anti-allergic and anti-inflammatory effects of Jacho (Lithospermum erythrorhizon). Methods : Macrophage 264.7 cells were pretreatment, macrophage were incubated with lipopolysaccharide(LPS) 100ng/ml for 12h ($TNF-{\alpha}$, IL-6) or 24h ($IL-1\beta$, IL-10) and media collectred and $TNF-{\alpha}$, IL-6, $IL-1{\beta}$, and IL-10 concentrations in supernatants were each measured by enzyme-linked immunosorbent assay. Concentrations of Jacho used were 50, 100, 250, 500, and $1000{\mu}g/ml$, and hydrocortisones used were 10-8, 10-7, 10-6, 10-5, and 10-4M. Results : Jacho showed inhibitory effect on $TNF-{\alpha}$ LPS-stimulated macrophage 264.7. The inhibitory effect was most significant in $250{\mu}g/ml$, and was not in a dose-dependent manner as in the hydrocortisone group Jacho also showed inhibitory effect on IL-6 by LPS-stimulated macrophage 264.7. The inhibitory effect was most significant in $1000{\mu}g/mL$, and increased in a roughly dose-dependent manner. Jacho and hydrocortisone showed contrary effect on $IL-1\beta$. Jacho obviously increased the expression of $IL-1\beta$, in alt five concentrations, End at the fewest concentration $(50{\mu}g/ml)$ the level of $IL-1\beta$, was highest. On the other hand, hydrocortisone was observed to have inhibitory effect on $IL-1\beta$, in all five concentrations. IL-10 was obviously inhibited by Jacho and hydrocortisone respectively in a roughly dose-dependent manner. Conclusions : By the findings of this experiment. Jacho was observed to have anti-allergic and anti-inflammatory effects through inhibiting pro-inflammatory cytokine $TNF-{\alpha}$ and IL-6, and might be one of the effective therapeutic regimens for allergic diseases.