• Journal of Life Science
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• v.32 no.6
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• pp.421-429
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• 2022

The expression of interleukin-1α (IL-1α) is elevated in monocytic cells, such as monocytes and macro-phages, within atherosclerotic arteries, yet the cellular molecules involved in cytokine upregulation remain unclear. Because peptidoglycan (PG), a major component of gram-positive bacterial cell walls, is detected within the inflammatory cell-rich regions of atheromatous plaques, it was investigated if PG contributes to IL-1α expression in monocytes/macrophages. Exposure of THP-1 monocytic cells to PG resulted in elevated levels of IL-1α gene transcripts and increased secretion of IL-1α protein. The transcription and secretion of IL-1α were abrogated by OxPAPC, an inhibitor of TLR2/4, but not by polymyxin B that inhibits lipopolysaccharide-induced TLR4 activation. To understand the molecular mechanisms of the inflammatory responses due to bacterial pathogen-associated molecular patterns (PAMPs) in diseased arteries, we attempted to determine the cellular factors involved in the PG-induced upregulation of IL-1α expression. Pharmacological inhibition of cell signaling pathways with LY294002 (a PI3K inhibitor), Akti IV (an inhibitor of Akt activation), rapamycin (an mTOR inhibitor), U0126 (a MEK inhibitor), SB202190 (a p38 MAPK inhibitor), SP6001250 (a JNK inhibitor), and DPI (a NOX inhibitor) also significantly attenuated the PG-mediated expression of IL-1α. These results suggest that PG induces the monocytic or macrophagic expression of IL-1α, thereby contributing to vascular inflammation, via multiple signaling molecules, including TLR2, PI3K/Akt/mTOR, and MAPKs.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.306-313
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• 2023

Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.46-46
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• 2003

Interleukin-10 (IL-10) is a homodimeric protein with a wide spectrum of anti-inflammatory and immune activities. It inhibits cytokine production and expression of immune surface molecules in various cell types. The transgenic mice carrying the human IL-10 gene in conjunction with the bovine $\beta$-casein promoter produced the human IL-10 in milk during lactation. Transgenic mice were generated using a standard method as described previously. To screen transgenic mice, PCR was carried out using chromosomal DNA extracted from tail or toe tissues with a primer set. In this study, stability of germ line transmission and expression of IL-10 gene integrated into host chromosome were monitored up to generation F15 of a transgenic line. When female mouse of generation F9 was crossbred with normal male, generation F9 to F15 mice showed similar transmission rates (66.0$\pm$20.13%, 61.5$\pm$16.66%, 41.1$\pm$8.40%, 40.7$\pm$20.34%, 61.3$\pm$10.75%, 49.2$\pm$18.82%, and 43.8$\pm$25.91%, respectively), implying that the IL-10 gene can be transmitted stably up to long term generation in the transgenic mice. For ELISA analysis, IL-10 expression levels were determined with an hIL-10 ELISA and a mIL-10 ELISA kit in accordance with the supplier's protocol. Expression levels of human IL-10 from milk of generation F9 to F13 mice were 3.6$\pm$1.20 mg/ml, 4.2$\pm$0.93 mg/ml, 5.7$\pm$1.46 mg/ml, 6.3$\pm$3.46 mg/ml, and 6.8$\pm$4.52 mg/ml, respectively. These expression levels are higher than in generation F1 (1.6 mg/ml) mice. We concluded that transgenic mice faithfully passed the transgene on their progeny and successively secreted target proteins into their milk through several generations, although there was a little fluctuation in the transmission frequency and expression level between the generations.

• Journal of Ginseng Research
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• v.28 no.2
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• pp.104-110
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• 2004

The aim of this study was to evaluate prospectively the impact of the red ginseng extract on circulating interleukin (IL) 2 and 10 in advanced gastric cancer during chemotherapy after operative treatment. Analysis of circulating IL-2 and 10 was performed in 50 patients with advanced gastric adenocarcinoma who underwent a curative surgery or with an unresectable gastric adenocarcinoma by using ELISA and monoclonal antibodies at preoperative day 1, postoperative months 1, and 3. Twenty-five patients as the control group, twenty-six patients as the non-ginseng (NG) group, and twenty-four patients as the ginseng (G) group were eligible in this study. All plasma IL-2 of the NG and G groups was significantly lower an that of the control group on preoperative 1 day. These values of the G group were more increase than these of the NG group during the postoperative chemotherapy. The mean value of serum IL-10 of the control group (0.608pg/ml) was significantly lower than that of the advanced gastric cancer patients including the NG (12.015 pg/ml) and G group (9.409 pg/ml) (p＜0.001). These values of the G group were reduced progressively during the postoperative chemotherapy. The mesh value of the G group were only close to that of the control group on postoperative months 3 (p=0.003). The number of patients who were enrolled in this study was relatively small to fully evaluate the immunologic effects of the red ginseng extract on circulating IL-2 and 10. Despite this limitation, these results suggest that the post-operative intake of the red ginseng extract have potential to improve earlier anti-cancer immunity with recovering IL-2 and reducing IL-10 from the depressed IL-2 and elevated IL-10 by gastric cancer during the postoperative chemotherapy. This study will be based on the future study to evaluate the anti-immunity of the red ginseng extract.

• Korean Journal of Psychosomatic Medicine
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• v.7 no.2
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• pp.196-202
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• 1999

The purpose of the study was to determine the effect of vitamin B complex on stress-induced immune alteration. 21 medical students participated in the study 4 weeks before an academic examination period(baseline), 2 weeks before the exam period and during the exam period. Among them, 10 subjects were given vitamin B complex for 4 weeks, and 11 were not given vitamin B during the whole period. Cell-mediated immune function was measured by lymphocyte proliferative response to phytohemagglutinin(PHA) and interleukin-2(IL-2) production. Global assessment of recent stress(GARS) scale and symptom checklist-90-revised(SCL-90-R) were used to measure the level of subjective stress and psychopathology. Vitamin group had significantly lower scores of anxiety scale on SCL-90-R than non-vitamin group. No significant differences were found in lymphocyte proliferative response to PHA and IL-2 production between vitamin and non-vitamin groups during each period. There were no significant differences in change of of each of the two immune parameters over time as well as between vitamin and non-vitamin groups. However, lymphocyte proliferative response to PHA was significantly increased over time. In conclusion, it was suggested that vitamin B complex is likely to decrease anxiety level, and that exam stress might enhance lymphocyte proliferation regardless of vitamin B.

• Journal of Periodontal and Implant Science
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• v.37 no.sup2
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• pp.409-426
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• 2007

세균성 치태는 치은의 염증과 치주 조직 파괴를 동반하는 치주염의 주요한 인자로서 치주 조직 건강을 유지하기 위하여 적절한 치태 조절이 필요하다. 본 논문의 목적은 12주 동안 만성 초기 및 중등도 치주염 환자에서 치은염에 대한 임상 지수의 감소, interleukin-6 (IL-6) 농도와 치주질환 원인균인 Prevotella intermedia (P. intermedia), Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans)에 대한 소니케어 전동 칫솔의 효과를 일반 칫솔과 비교해 보고자 하는 데 있다. 총 82명의 환자를 선택하였으며, 30명은 일반 칫솔, 52명은 소니케어 전동 칫솔 군으로 분류하여 칫솔질 교육을 실시하였다. 전악을 전치부와 구치부로 나누어 초진, 1, 4, 12주에서의 치태, 치은 지수 및 탐침 시 출혈 여부를 조사하였으며, 가장 깊은 치주낭 탐침을 보이는 치아 3개를 선택하여 탐침 깊이와 부착 정도를 측정하였고, 선택된 치아에서 초진, 1, 12주에 채취된 샘플을 통해 치은열구액 내의 IL-6 농도와 P. intermedia, A. actinomycetemcomitans의 CT값을 추가적으로 조사하여 다음과 같은 결과를 얻었다. 1 소니케어 전동 칫솔과 일반 칫솔군 모두 치은 염증을 나타내는 임상 지수 (치태지수, 치은지수, 탐침 시 출혈)는 12주 기간 동안 유의한 감소 (p<0.05)를 보였으나, 전동 칫솔 군에서 통계학적으로 더욱 유의하게 (p<0.05) 나타났다. 2. 전치부를 제외한 구치부 치아에서 소니케어 전동 칫솔군은 12주 기간 동안 탐침 시 출혈의 감소가 통계학적으로 유의하게 (p<0.05) 나타났다. 3. 가장 깊은 치주낭 탐침 깊이를 보이는 3개의 선택된 치아에서 치주낭 탐침 깊이와 부착 정도는 두 군 모두 초진에 비해 유의한 감소 (p<0.05)를 보였다. 퍼센트 변화 비교에서 치주낭 탐침 깊이는 소니케어 전동 칫솔군이 $18.47{\pm}10.05%$, 일반 칫솔군이 $14.19{\pm}8.16%$로, 부착 정도는 소니케어 전동 칫솔군이 $24.26{\pm}12.51%$, 일반 칫솔군이 $15.65{\pm}9.92%$로 각각 나타났으나, 군 간 통계적 유의차는 보이지 않았다. 4. 치은열구액의 IL-6 농도는 두 군 모두 12주 기간 동안 통계적으로 유의한 감소 (p<0.05)를 나타내었다. 퍼센트 변화 비교에서 전동 칫솔군은 51%, 일반 칫솔군은 37%로 각각 나타났으나, 군 간 통계적 유의차는 보이지 않았다. 5. Prevotella intermedia, Actinobacillus actinomycetemcomitans의 관찰에서 두 군 모두 유의한 차이는 없었다. 위 결과를 통해 본 연구에서는 소니케어 전동 칫솔의 사용이 일반 칫솔에 비하여 만성 초기 및 중등도 치주염 환자에서 치태의 제거, 치은 염증 및 임상 지수의 감소에 유의한 효과가 있으며 IL-6의 감소 경향에도 효과가 있음을 관찰하였다.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.3
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• pp.249-258
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• 2018

Airborne pollution causes oxidative damage, inflammation, and premature aging of skin. Resveratrol is a polyphenol compound that has various biological activities such as antioxidant, anti-inflammation, and anti-melanogenic activities but it is unstable to heat and light. Resveratryl triacetate (RTA) is a new cosmetic ingredient that is more stable than resveratrol and its skin safety and whitening efficacy have been reported previously. The purpose of this study was to examine the effects of resveratrol and resveratryl triacetate (RTA) on the inflammatory responses of human epidermal keratinocytes (HEKs) exposed to airborne particulate matters with a diameter of < $10{\mu}m$ (PM10). Cultured HEKs were exposed to PM10 in the absence or presence of resveratrol and RTA. Assays were undertaken to determine cell viability, the production of reactive oxygen species (ROS), and the expression of inflammatory cytokines. PM10 treatment decreased cell viability, and increased the expression of pro-inflammatory cytokines such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and interleukin-8 (IL-8). Resveratrol and RTA reduced cell death and ROS production induced by PM10. PM10-induced mRNA expression of the inflammatory cytokines was either attenuated (IL-6), or enhanced ($IL-1{\beta}$), or unaffected ($TNF-{\alpha}$ and IL-8) by resveratrol and RTA. PM10-induced IL-6 protein expression was attenuated by resveratrol and RTA. This study suggests that resveratrol and RTA have activities regulating cell damage and inflammatory responses of the skin exposed to airborne particulate matters.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.475-480
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• 2014

We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the $IL-1{\alpha}$ gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of $IL-1{\alpha}$. Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and $IL-1{\alpha}$. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and $IL-1{\alpha}$ induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of $IL-1{\alpha}$. These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of $IL-1{\alpha}$ in monocytic cells via multiple signaling pathways.

• BMB Reports
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• v.45 no.7
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• pp.414-418
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• 2012

Triglycerides (TG) are implicated in the development of atherosclerosis through formation of foam cells and induction of macrophage cell death. In this study, we report that addition of exogenous TG induced cell death in phorbol 12-myristate 13-acetate-differentiated THP-1 human macrophages. TG treatment induced a dramatic decrease in interleukin-$1{\beta}$ (IL-$1{\beta}$) mRNA expression in a dose- and time-dependent manner. The expression of granulocyte macrophage colony-stimulating factor and platelet endothelial cell adhesion molecule remained unchanged. To identify signaling pathways involved in TG-induced downregulation of IL-$1{\beta}$, we added p38 MAPK, protein kinase C (PKC) or c-Raf1 specific inhibitors. We found that inhibition of p38 MAPK alleviated the TG-induced downregulation of IL-$1{\beta}$, whereas inhibition of PKC and c-Raf1 had no effect. This is the first report showing decreased IL-$1{\beta}$ expression during TG-induced cell death in a human macrophage line. Our results suggest that downregulation of IL-$1{\beta}$ expression by TG-treated macrophages may play a role during atherogenesis.

• YAKHAK HOEJI
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• v.47 no.5
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• pp.311-318
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• 2003

Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.