• Tuberculosis and Respiratory Diseases
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• 제45권6호
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• pp.1167-1177
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• 1998

연구배경 : 결핵은 우리나라에서 아직도 흔하게 발생하는 질환으로 세포면역반응에 의해 육아종이 형성되며, 이 과정에서 대식세포가 분비하는 tumor necrosis factor-alpha (TNF-$\alpha$), Th1 세포가 생성하는 gamma-Interferon (INF-$\gamma$), 내피 세포가 표현하는 intercelluar adhesion molecule-1 (ICAM-1)이 중요한 역할을 할 것이라고 생각되었다. 방 법 : 저자들은 결핵의 경중(輕重)과 이러한 물질들이 관련이 있는가를 알아보기 위하여, 환자의 혈액을 채취하여 TNF-$\alpha$, INF-$\gamma$를 radioimmuno assay(RIA)로, ICAM-1이 혈액으로 유리된 형태인 sICAM-1을 enzyme linked immunosolvent assay(ELISA)로 각각 측정하였다. 또한 화학 요법에 따른 변화를 알기 위해 치료 시작후 6개월 시점에서 다시 추적검사를 실시하였다. 결 과 : TNF-$\alpha$, INF-$\gamma$, sICAM-1은 중등증과 중증의 결핵에서는 의미 있게 증가하였고, 경증에서는 의의가 없었다. 6개월간의 항결핵 치료후, sICAM-1은 임상경과에 동반하여 의미있는 감소를 보였지만. TNF-$\alpha$, INF-$\gamma$에서는 감소는 있었지만 의의는 없었다. 결 론 : 본 실험 결과 결핵의 세포 면역 매개과정에는 TNF-$\alpha$와 INF-$\gamma$가 매우 중요한 역할을 하며, 그 반응 정도가 질병의 병기에 따라 심할수록 많이 증가함을 관찰하였다. ICAM-1은 TNF-$\alpha$와 INF-$\gamma$ 농도와 비례하여 sICAM-1이 증가하였고, 질병의 병기에 따라 농도의 차이가 있을뿐 아니라, 치료경과에 비례하여 농도변화를 보여, 질병의 할동성을 나타내는 것 외에 치료 경과를 나타내는 지시자로서의 가능이 있을 것으로 생각된다.

• Journal of Microbiology and Biotechnology
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• 제23권10호
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• pp.1357-1364
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• 2013

Human skin is continuously exposed to ultraviolet (UV)-induced photoaging. UVA increases the activity of MMP-1 in dermal fibroblasts through mitogen-activated protein kinase (MAPK), p38, signaling. The irradiation of keratinocytes by UVA results in the secretion of the inflammatory cytokine, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and the stimulation of MMP-1 in normal human dermal fibroblasts (NHDFs). Lipoteichoic acid (LTA) is a component of the cell wall of gram-positive Lactobacillus spp. of bacteria. LTA is well known as an anti-inflammation molecule. LTA of the bacterium Lactobacillus plantarum has an anti-photoaging effect, but the potential anti-photoaging effect of the other bacteria has not been examined to date. The current study showed that L. sakei LTA (sLTA) has an immune modulating effect in human monocyte cells. Our object was whether inhibitory effects of sLTA on MMP-1 are caused from reducing the MAPK signal in NHDFs. It inhibits MMP-1 and MAPK signaling induced by UVA in NHDFs. We also confirmed effects of sLTA suppressing TNF-${\alpha}$ inducing MMP-1 in NHDFs.

• Molecules and Cells
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• 제26권6호
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• pp.583-589
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• 2008

In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-$1{\alpha}$ ($MIP-1{\alpha}$) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. The effects of rosmarinic acid were investigated in BMDCs with respect to the following; cytotoxicity, surface molecule expression, dextran-FITC uptake, cell migration, chemokine gene expression, and the MAPK signaling pathway. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86, MHC class I, and MHC class II in LPS-stimulated mature BMDCs, and rosmarinic acid-treated BMDCs were found to be highly efficient with regards to antigen capture via mannose receptor-mediated endocytosis. In addition, rosmarinic acid reduced cell migration by inducing the expression of a specific chemokine receptor on LPS-induced mature BMDCs. Rosmarinic acid also significantly reduced the expressions of MCP-1 and $MIP-1{\alpha}$ induced by LPS in BMDCs and inhibited LPS-induced activation of MAPK and the nuclear translocation of $NF-{\kappa}B$. These findings broaden current perspectives concerning our understanding of the immunopharmacological functions of rosmarinic acid, and have ramifications that concern the development of therapeutic drugs for the treatment of DC-related acute and chronic diseases.

• IMMUNE NETWORK
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• 제6권1호
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• pp.13-19
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• 2006

Background: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti inflammatory way. Methods: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. Results: Re combinant human G-CSF significantly inhibited LPS-induced TNF-${\alpha}$ mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and intercellular adhesion molecule-1 in TNBS colitis. Conclusion: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

• 대한의생명과학회지
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• 제13권4호
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• pp.279-285
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• 2007

Although retinoic acid has been known as either anti-inflammatory or pro-inflammatory molecule, depending on the cell type, its exact role in mature human neutrophils has not been fully explored. In this study, we investigate the effects of retinoic acid on neutrophil apoptosis and the associated mechanism and found that 9-cis retinoic acid (9CRA) significantly inhibits the spontaneous apoptosis of neutrophils. Its effect is increased by co-treatment with $TNF-\alpha$ (P<0.05). The 9CRA-induced inhibition is blocked by the following enzyme inhibitors: Ly 294002, phosphoinoside (PI)-3 kinase inhibitor, U73122, a phospholipase C (PLC) inhibitor, PP2, Src family protein inhibitor, SB202190, p38 MAPK inhibitor, and BAY-11-7085, NF-kB inhibitor. This study also demonstrates that all-trans retinoic acid suppresses spontaneous apoptosis, similar to the mechanism of inhibition exhibited by 9CRA. Phosphorylation of p38 MAPK decreases by 9CRA treatment. $Ik-B{\alpha}$ is degraded until 30 minutes after a time-dependent 9CRA treatment, but degradation can be inhibited by Ly 294002. These results indicate that 9CRA decreases p38 MAPK activation, induces NF-kB activation via PI-3 kinase, and also blocks cleavage of caspase 3. As these findings suggest, 9CRA has a molecular mechanism which may help pro-inflammatory response by blocking neutrophil apoptosis.

• Journal of Periodontal and Implant Science
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• 제43권4호
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• pp.191-197
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• 2013

Purpose: Nitric oxide (NO) is a short-lived bioactive molecule that is known to play an important role in the pathogenesis of periodontal disease. In the current study, we investigated the effect of the flavonoid quercetin on the production of NO in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen related to inflammatory periodontal disease, and tried to elucidate the underlying mechanisms of action. Methods: LPS was isolated from P. intermedia ATCC 25611 cells by the standard hot phenol-water method. The concentration of NO in cell culture supernatants was determined by measuring the accumulation of nitrite. Inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) protein expression, phosphorylation of c-Jun N-terminal kinase (JNK) and p38, inhibitory ${\kappa}B$ $(I{\kappa}B)-{\alpha}$ degradation, and signal transducer and activator of transcription 1 (STAT1) phosphorylation were analyzed via immunoblotting. Results: Quercetin significantly attenuated iNOS-derived NO production in RAW246.7 cells activated by P. intermedia LPS. In addition, quercetin induced HO-1 protein expression in cells activated with P. intermedia LPS. Tin protoporphyrin IX (SnPP), a competitive inhibitor of HO-1, abolished the inhibitory effect of quercetin on LPS-induced NO production. Quercetin did not affect the phosphorylation of JNK and p38 induced by P. intermedia LPS. The degradation of $I{\kappa}B-{\alpha}$ induced by P. intermedia LPS was inhibited when the cells were treated with quercetin. Quercetin also inhibited LPS-induced STAT1 signaling. Conclusions: Quercetin significantly inhibits iNOS-derived NO production in murine macrophages activated by P. intermedia LPS via anti-inflammatory HO-1 induction and inhibition of the nuclear factor-${\kappa}B$ and STAT1 signaling pathways. Our study suggests that quercetin may contribute to the modulation of host-destructive responses mediated by NO and appears to have potential as a novel therapeutic agent for treating inflammatory periodontal disease.

• Nutrition Research and Practice
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• 제13권1호
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• pp.3-10
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• 2019

BACKGROUND/OBJECTIVES: The $NAD^+$ precursor nicotinamide riboside (NR) is a type of vitamin $B_3$ found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; $250{\mu}M$) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR ($10{\mu}M$ and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.

• 한국미생물·생명공학회지
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• 제51권4호
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• pp.465-473
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• 2023

본 연구에서는 볶음 쓴메밀 '황금미소' 분말을 첨가한 배지에 단일 및 복합 프로바이오틱스를 배양하여 쓴메밀 주요성분인 rutin의 quercetin으로 생물전환능과 이의 항산화, 항염 생리활성을 평가하였다. 단일 균주 배양 시 생물전환률은 각각 LP3 89%, SL6 84%, ST3 87%로 보였으며, 프로바이오틱스 3종 복합 배양 시 97%로 단일균주와 비교하여 유의적으로 증가하였다. 배양 전 배양액과 3종의 단일 균주 배양 및 복합 균주 배양액에서 DPPH, ABTS 분석 결과, 3종 프로바이오틱스 복합 균주 배양 시 항산화 활성이 유의적으로 증가하였다. 또한, LPS에 의해 유도된 RAW 264.7 세포의 염증반응 분석결과, 산화질소 생성능, iNOS와 TNF-α의 mRNA 발현, IL-6와 IL-4 사이토카인 분비능이 3종 프로바이오틱스 복합 균주 배양 시 가장 우수한 효능을 확인하였다. 이상의 결과는 쓴메밀 혹은 rutin이 풍부한 천연물과 이의 생물전환이 가능한 CBT LP3, SL6, ST3의 복합 섭취가 rutin 성분의 quercetin으로 전환 및 항염, 항산화 등의 생리활성 효력 증대에 영향을 줄 수 있을 것으로 판단된다.

• 한국자원식물학회지
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• 제25권1호
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• pp.1-6
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• 2012

본 연구는 우엉추출물의 항염증효과를 측정하였다. 인간 유래 폐상피세포 A549를 이용하여 염증반응을 유발하고 유지시키는데 중요한 역할을 나타낸다고 알려진 ICAM-1의 억제적 조절 효과를 평가하였으며, 염증매개인자로 알려진 NO와 이의 생성에 영향을 미치는 iNOS의 발현조절에서도 억제효과가 있음을 확인하였다. 또한, 우엉추출물이 인간각질형성세포주의 세포증식에 효과가 있음을 나타내었다. 본 연구에서 사용되는 폐상피세포는 호흡기질환의 천식 등의 알러지 및 만성염증연구에 주로 활용되고 있으며, 각질형성세포는 아토피 피부염의 만성 염증반응에서 주요하게 확인하는 요소이다. 따라서 본 연구결과에서 나타난 우엉추출물의 항염증 효과는 다양한 염증반응에서도 특히, 알러지 및 아토피 피부염 질환을 더욱 악화시키는 만성 염증에 있어서 우엉추출물이 유용한 소재로 사용될 수 있음을 시사한다고 할 수 있다.

• Fisheries and Aquatic Sciences
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• 제21권6호
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• pp.16.1-16.7
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• 2018

Background: Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content. Methods: In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells. S. horneri crude extract was fractionated with organic solvents, namely, water ($H_2O$), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solvent-partitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting. Results: All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography. Except $H_2O$ fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Conclusion: Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules.