• The Korean journal of internal medicine
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• 제33권6호
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• pp.1103-1110
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• 2018

Background/Aims: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. Methods: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin $1{\beta}$ (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor ${\alpha}$ (TNFA) genes of patients with AP were compared to those of normal controls. Results: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN -1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (-118C>T, c47+242C>T, +3954C/T, and -598T>C) and TNFA (-1211T>C, -1043C>A, -1037C>T, -488G>A, and -418G>A). Conclusions: IL1RN -1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.435-441
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• 1998

We examined effects of interleukin $1{\alpha}$ ($IL1{\alpha}$) and phorbol 12, 13 dibutyrate (PDB), an activator of protein kinase C, on mRNA for Prostaglandin H synthase (PGHS) and prostanoid production in cultured ovine meningeal fibroblasts. Immuno- and morphologically-identified fibroblasts were derived from cerebral cortex and white matter from fetal lambs (approximately 120 days gestation) and grown to confluence on glass coverslips in 12 well plates. Levels of prostaglandin $F_{2{\alpha}}$ and the stable hydrolysis product of prostacyclin (i.e., $6-keto-PGF_{1{\alpha}}$) were determined using enzyme immunoassay. Relative amounts of mRNA were determined by in situ hybridization using ovine cDNA for PGHS1. $IL1{\alpha}$ (10 ng/ml) increased mRNA levels over baseline by $62{\pm}19%$ (p＜0.05) at 60 min., $37{\pm}12%$ (NS) at 120 min., and $36{\pm}18%$ (NS) at 240 min (n=12). Levels of $6-keto-PGF_{1{\alpha}}$ were $148{\pm}18%$ pg/ml during baseline, $246{\pm}41%$ pg/ml at 60 min., $248{\pm}40%$ pg/ml at 120 min., and $259{\pm}62%$ pg/ml at 240 min (all p＜0.05) (n=12). $PGF_{2{\alpha}}$ was increased although it wasn't statistically significant. However, $IL1{\alpha}$ decreased $PGE_2$ level significantly (all p＜0.05). PDB $(10^{-6}M)$ increased mRNA levels over baseline by $25{\pm}6%$ after 30 min., $40{\pm}6%$ after 60 min., and $20{\pm}8%$ after 90 min. (n=9) (all p＜0.05). Levels of $6-keto-PGF_{1{\alpha}}$ were $200{\pm}43%$ pg/ml during baseline, $202{\pm}43%$ pg/ml after 30 min. (NS), $268{\pm}58%$ pg/ml after 60 min. (p＜0.05), and $296{\pm}60%$ pg/ml after 90 min. (p＜0.05) (n=9). Levels of $PGF_{2{\alpha}}$ were $178{\pm}26%$ pg/ml during baseline, $300{\pm}30%$ pg/ml after 30 min., $299{\pm}35%$ pg/ml after 60 min., and $355{\pm}32%$ pg/ml after 90 min (all p＜0.05) (n=6). Actinomycin-D (1 mg/ml) prevented increases in mRNA, $6-keto-PGF_{1{\alpha}}$, and $PGF_{2{\alpha}}$ at 60 min. for both $IL1{\alpha}$ and PDB. We conclude that cerebral fibroblasts are avid producers of prostanoids, and that enhanced production of PGHS is responsible for augmented $PGF_{2{\alpha}}$ and prostacyclin production in the presence of an activator of protein kinase C and for decreased $PGE_2$ and increased prostacyclin production in the presence of $IL1{\alpha}$.

• International Journal of Oral Biology
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• 제45권2호
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• pp.64-69
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• 2020

Short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are secondary metabolites produced by anaerobic fermentation of dietary fibers in the intestine. Intestinal SCFAs exert various beneficial effects on intestinal homeostasis, including energy metabolism, autophagy, cell proliferation, immune reaction, and inflammation, whereas contradictory roles of SCFAs in the oral cavity have been reported. Herein, we found that low and high concentrations of SCFAs induce differential regulation of intracellular Ca²⁺ mobilization and expression of pro-inflammatory cytokines, such as interleukin (IL)-6 and IL-8, respectively, in gingival fibroblast cells. Additionally, cell viability was found to be differentially regulated in response to low and high concentrations of SCFAs. These findings demonstrate that the physiological functions of SCFAs in various cellular responses are more likely dependent on their local concentration.

• 대한의생명과학회지
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• 제29권3호
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• pp.137-143
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• 2023

Inflammation plays an important role in immune system's response to tissue injury and biological stimuli. However, excessive inflammation can cause tissue damage. Therefore, the development of naturally derived anti-inflammatory agents have received broad attention. In this study, we investigated the anti-inflammatory mechanism of Rubi Fructus (RF) extract on the mast cell-mediated inflammatory response. To determine the regulatory mechanism of RF in inflammatory reaction, we evaluated the effects of RF on secretion of interleukin (IL)-8, IL-6 and tumor necrosis factor (TNF)-α and activation of nuclear factor-κB (NF-κB) and caspase-1 in activated human mast cells-1 (HMC-1). The results showed that RF attenuated IL-8, IL-6 and TNF-α secretion in a concentration-dependent manner. Moreover, RF significantly attenuated caspase-1and NF-κB activation in activated HMC-1. Conclusively, the present results provide evidence that RF may be a promising agent for anti-inflammatory therapy.

• 생명과학회지
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• 제21권5호
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• pp.678-683
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• 2011

본 연구에서는 울릉도 특산 약용 작물 추출물이 항염증에 대한 실험연구가 이루어져 있지 않은 것에 착안하여 LPS에 의해 활성화된 대식세포로부터 유도되는 염증반응에 대한 억제효과를 조사하였다. 울릉도 자생 식물인 곰취, 미역취, 삼나물의 세가지 식물 추출물을 이용하여 피부 염증에 대하여 연구를 하였다. 산화질소와 cytokine의 생산은 면역세포의 대표적인 염증인자이다. 세포는 LPS 처리 후 한 시간 뒤에 곰취, 미역취, 삼나물 70% 아세톤 추출물을 처리를 하였다. 세포 독성이 나타나지 않는 농도인 1, 10, 100 ug/ml를 사용하였다. 곰취, 미역취, 삼나물 70% 아세톤 추출물은 NO, $PGE_2$, TNF-${\alpha}$, IL-1${\beta}$, IL-6, iNOS, COX-2의 생성을 저해 시켰다. $PGE_2$는 100 ug/ml의 농도에서 60%에 가까운 저해율을 나타내었다. iNOS와 COX-2 역시 100 ug/ml의 농도에서 각각 54%, 65%가 저해가 되었다. 게다가 곰취, 미역취, 삼나물 70% 아세톤 추출물은 염증성 사이토 카인인 TNF-${\alpha}$, IL-1${\beta}$, IL-6의 생성을 감소 시켰다. 이러한 결과로 곰취, 미역취, 삼나물 추출물은 염증 예방과 치료에 효과적임을 확인할 수 있었다.

• 생명과학회지
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• 제23권1호
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• pp.55-62
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• 2013

본 연구에서는 홍화자 추출물이 항염증에 대한 실험연구가 이루어져 있지 않은 것에 착안하여 LPS에 의해 활성화된 대식세포로부터 유도되는 염증반응에 대한 억제효과를 조사하였다. 홍화자 추출물을 이용하여 피부 염증에 대하여 연구를 하였다. 산화질소와 cytokine의 생산은 면역세포의 대표적인 염증인자이다. 세포는 LPS 처리 후 한 시간 뒤에 홍화자 추출물을 처리를 하였다. 세포 독성이 나타나지 않는 농도인 5, 10, 25 및 50 ${\mu}g/ml$를 사용하였다. 홍화자의 에틸아세테이트 분획물은 NO, $PGE_2$, TNF-${\alpha}$, IL-$1{\beta}$, IL-6, iNOS, COX-2의 생성을 저해 시켰다. $PGE_2$는 50 ${\mu}g/ml$의 농도에서 60%에 가까운 저해율을 나타내었다. iNOS와 COX-2 역시 ${\mu}g/ml$의 농도에서 각각 54%, 65%가 저해가 되었다. 게다가 홍화자 에틸아세테이트 분획물은 염증성 사이토카인인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 생성을 감소 시켰다. 이러한 결과로 홍화자 추출물은 염증 예방과 치료에 효과적임을 확인 할 수 있었다.

• 생명과학회지
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• 제23권1호
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• pp.38-43
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• 2013

CopA3를 이용하여 피부 염증에 대하여 연구를 하였다. 산화질소와 cytokine의 생산은 면역세포의 대표적인 염증인자이다. 세포는 LPS 처리 후 한 시간 뒤에 CopA3를 처리하였다. 세포 독성이 나타나지 않는 농도인 5, 25, 50, 100 ${\mu}g/ml$를 사용하였다. CopA3는 NO, TNF-${\alpha}$, IL-$1{\beta}$, IL-6, iNOS, COX-2의 생성을 저해 시켰다. iNOS와 COX-2 역시 100 ${\mu}g/ml$의 농도에서 각각 54%, 65%가 저해가 되었다. 게다가 CopA3는 염증성 사이토 카인인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 생성을 감소 시켰다. 이러한 결과로 CopA3는 염증 예방과 치료에 효과적임을 확인 할 수 있었다.

• Journal of Nutrition and Health
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• 제52권3호
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• pp.243-249
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• 2019

본 연구에서는 LPS로 활성화된 마우스 비장세포에서 Platycodin D가 함유된 홍도라지 추출물의 항염증 효능을 알아보기 위하여 비장세포 증식능과 NO 생성 및 염증 관련 사이토카인을 측정하였다. 결과를 요약하면 다음과 같다. 1. 마우스 비장세포에 $1{\mu}g/mL$ 농도의 LPS를 처리하였을 때 비장세포의 증식능이 3배 이상 증가하였으며 홍도라지 추출물 처리 시 증가 된 증식능이 유의하게 감소되었다. 2. 마우스 비장세포에 $1{\mu}g/mL$ 농도의 LPS를 처리하였을 때 비장세포의 NO생성이 증가하였으며, 홍도라지 추출물 처리 시 농도 의존적으로 증가 된 NO생성이 줄어들었다. 3. 마우스 비장세포에 $1{\mu}g/mL$ 농도의 LPS를 처리하였을 때 염증관련 사이토카인 IL-6와 항염증 사이토카인 IL-10 분비가 증가되었으며, 홍도라지 추출물 처리 시 농도 의존적으로 증가 된 IL-6의 분비가 감소되었다. IL-10 분비에는 유의적인 차이가 없었다. 위의 결과를 종합하여 볼 때, 본 연구는 홍도라지 추출물이 ex vivo 실험을 통해 항염증관련 인자들의 조절을 통하여 과민면역반응을 효과적으로 억제한다는 근거를 확인하였다. 이에 동물실험과 인체적용시험을 통해 홍도라지 추출물의 과민면역반응 억제 효능에 관한 후속 연구가 필요할 것으로 사료된다.

• 대한한방부인과학회지
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• 제21권1호
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• pp.39-54
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• 2008

Purpose: The purpose of this study was to investigate the anti-inflammatory effects of the water extract of Omisodokeum (OMSDE) on peritoneal macrophages, Methods: To verify the anti-inflammatory mechanism of OMSDE, the activation of nuclear $factor-{\kappa}B$ $(NF-{\kappa}B)$ and the phosphorylation of MAPK were examined. Results: The extract of OMSDE suppressed the production of LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6 and IL-12 in the macrophages. OMSDE inhibited the degradation of inhibitory ${\kappa}B-{\alpha}$ $(I{\kappa}B-{\alpha})$ and it suppressed the activation of extracellular signal-regulated kinase (ERK 1/2) but didn't inhibit c-Jun N-terminal kinase (JNK) and p38, indicating that OMSDE may inhibit the pro-inflammatory cytokine production process by inhibiting the activation of $NF-{\kappa}B$ and ERK 1/2. Furthermore, OMSDE inhibited the production of interferon $(IFN)-{\beta}$ but didn't inhibit of $IFN-{\alpha}$ in the LPS-stimulated macrophages through the down-regulation of interferon regulatory factor (IRF)-1 and IRF-7. The Oral administration of OMSDE inhibited LPS-induced endotoxin shock and the production of $TNF-{\alpha}$ in serum but didn't inhibit of $IL-1{\beta}$ and IL-6. Conclusion: These results suggest that OMSDE may be effective in the prevention and treatment of inflammatory diseases.

• 한방안이비인후피부과학회지
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• 제23권1호
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• pp.44-58
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• 2010

Silibinin is the major active molecule of silymarin, the mixture of flavonolignans extracted from Cirsium japonicum (CJ). It has been used for treatment of hepatitis and inflammation related diseases. The aim of this study was to prove whether Silibinin has effectiveness for allergic inflammation. Silibinin processes the inflammatory reaction in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (PMA plus A23187) stimulated human mast cell line (HMC-1). Its effect was examined by ELISA, RT-PCR, Western blot, and Luciferase assay. The results were Silibinin inhibited the expression of histamine, TNF-$\alpha$ (tumor necrosis factor-$\alpha$), IL-6 (interleukin-6), and IL-8 (interleukin-8). Silibinin suppressed NF-${\kappa}B$ (nuclear factor kappa B) activation in stimulated HMC-1 (human mast cell-1). This effect was mediated through inhibition of phosphorylation and degradation of $IkB{\alpha}$, an inhibitor of NF-kB. Silibinin significantly inhibited induction of NF-kB promoter mediated Luciferase assay. These results suggest that Silibinin has a potential molecule for therapy of mast cell-derived allergic inflammatory diseases.