• 운동과학
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• 제26권3호
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• pp.223-228
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• 2017

PURPOSE: This study investigated the protective role of high-intensity interval training against acute liver injury induced by D-galactosamine (D-Gal)/lipopolysaccharide (LPS). METHODS: A total of 30 male BALB/c mice aged 5-week were randomly assigned to high-intensity, interval training group (EX, n=10) or control group in cage (Non-EX, n=20) for 10 weeks. Peritoneal injection of D-Gal (700 mg/kg body weight) and LPS ($10{\mu}g/kg$ body weight) was applied to induce acute liver injury, and liver tissue was harvested 6 hours after the injection. Hematoxylin and Eosin (H&E) staining was used for liver histology. Real-time PCR was used to quantify expression of pro-inflammatory and anti-inflammatory genes in the liver. RESULTS: The liver histology showed that D-Gal/LPS treatment resulted in hepatic damage and increased number of neutrophils in conjunction with upregulation of hepatic IL-6 and $TNF-{\alpha}$ mRNAs and downregulation of hepatic $PPAR{\alpha}$ and SIRT1 mRNAs. On the other hand, the 10-week interval training resulted in a significant improvement in cardiorespiratory fitness assessed as run time to exhaustion on a treadmill. In addition, the interval training attenuated the D-Gal/LPS-induced liver damage and increased number of neutrophil in conjunction with downregulation of hepatic IL-6 and $TNF-{\alpha}$ mRNAs and upregulation of hepatic $PPAR{\alpha}$ and SIRT1 mRNAs. CONCLUSIONS: This study suggests that high-intensity interval training suppresses the D-Gal and LPS-induced acute liver damage and inflammatory responses.

• Nutrition Research and Practice
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• 제10권4호
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• pp.377-384
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• 2016

BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol ($25-200{\mu}M$) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.

• Journal of Ginseng Research
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• 제32권4호
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• pp.315-323
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• 2008

In the previous studies, we isolated the compound K rich fractions (CKRF) and showed that CKRF inhibited Toll-like receptor (TLR) 4- or TLR9-induced inflammatory signaling. To extend our previous studies,1) we investigated the molecular mechanisms of CKRF in the TLR4-associated signaling via nuclear factor (NF)-${\kappa}B$, and in vivo role of CKRF for induction of tolerance in lipopolysaccharide (LPS)-induced septic shock. In murine bone marrow-dervied macrophages, CKRF significantly inhibited the induction of mRNA expression of proinflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, CKRF significantly attenuated the transcriptional activities of TLR4/LPS-induced NF-${\kappa}B$. Nuclear translocation of NF-${\kappa}B$ in response to LPS stimulation was significantly abrogated by pre-treatment with CKRF. Furthermore, CKRF inhibited the recruitment of p65 to the interferon-sensitive response element flanking region in response to LPS. Finally, oral administration of CKRF significantly protected mice from Gram-negative bacterial LPS-induced lethal shock and inhibited systemic inflammatory cytokine levels. Together, these results demonstrate that CKRF modulates the TLR4-dependent NF-${\kappa}B$ activation, and suggest a therapeutic role for Gram-negative septic shock.

• 대한의생명과학회지
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• 제25권1호
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• pp.92-98
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• 2019

Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.

• Journal of Dental Anesthesia and Pain Medicine
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• 제22권5호
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• pp.369-376
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• 2022

Background: Nonobstetric surgery is sometimes required during pregnancy, and neck abscess or facial bone fracture surgery cannot be postponed in pregnant women. However, dental surgery can be stressful and can cause inflammation, and the inflammatory response is a well-known major cause of preterm labor. Propofol is an intravenous anesthetic commonly used for general anesthesia and sedation. Studies investigating the effect of propofol on human amnion are rare. The current study investigated the effects of propofol on lipopolysaccharide (LPS)-induced inflammatory responses in human amnion-derived WISH cells. Methods: WISH cells were exposed to LPS for 24 h and co-treated with various concentrations of propofol (0.01-1 ㎍/ml). Cell viability was measured using the MTT assay. Nitric oxide (NO) production was analyzed using a microassay based on the Griess reaction. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE 2), p38, and phospho-p38 was analyzed using western blotting. Results: Propofol did not affect the viability and NO production of WISH cells. Co-treatment with LPS and propofol reduced COX-2 and PGE₂ protein expression and inhibited p38 phosphorylation in WISH cells. Conclusion: Propofol does not affect the viability of WISH cells and inhibits LPS-induced expression of inflammatory factors. The inhibitory effect of propofol on inflammatory factor expression is likely mediated by the inhibition of p38 activation.

• Biomolecules & Therapeutics
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• 제23권1호
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• pp.90-97
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• 2015

Water chestnut (Trapa japonica Flerov.) is an annual aquatic plant. In the present study, we showed that the treatment of water chestnut extracted with boiling water resulted in a significant increase 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and decrease the intracellular $H_2O_2$-induced accumulation of reactive oxygen species. In addition, water chestnut extract (WCE) inhibited lipopolysaccharide (LPS)-induced nitric oxide production and suppressed mRNA and protein expression of the inducible nitric oxide synthase gene. The cytokine array results showed that WCE inhibited inflammatory cytokine secretion. Also, WCE reduced tumor necrosis factor-${\alpha}$- and interleukin-6-induced nuclear factor-${\kappa}B$ activity. Furthermore, during sodium lauryl sulfate (SLS)-induced irritation of human skin, WCE reduced SLS-induced skin erythema and improved barrier regeneration. These results indicate that WCE may be a promising topical anti-inflammatory agent.

• 약학회지
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• 제59권6호
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• pp.251-258
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• 2015

Aim of the present study was to investigate whether methanol extract from the leaves of Staphylea bumalda could be used to suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage cell lines, Raw 264.7 cells. The extract reduced nitric oxide (NO), cyclooxigenase-2 (COX-2) and pro-inflammatory cytokines production from LPS-stimulated Raw 264.7 cells. These inhibitory effects were associated with decreases in the phosphorylation of MAP kinases and the activity of $NF{\kappa}B$ signal pathways. Our results indicate that Staphylea bumalda significantly inhibits the inflammatory activity of activated macrophages, suggesting that Staphylea bumalda could be a potential candidate for the treatment of inflammatory disease.

• Korean Journal of Acupuncture
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• 제36권3호
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• pp.162-170
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• 2019

Objectives : Increasing evidence suggests that parasympathetic vagus nerve activity plays a role in modulating acupuncture-induced anti-inflammatory reaction, but the function of sympathetic nerve is not known. Here, we investigated whether splanchnic sympathetic nerve activity was involved in the regulation of splenic expression of $TNF-{\alpha}$ mRNA by electroacupuncture (EA) in LPS-injected animals. Methods : DiI was injected into the stomach or celiac ganglion (CG) for retrograde labeling of the target tissues. EA was given at ST36 and the electrical stimulation on the sciatic nerve in LPS-injected mice. c-Fos signals in the tissues were analyzed by immunofluorescence staining, and $TNF-{\alpha}$ mRNA was analyzed by real-time PCR. Results : Application of EA at ST36 or electrical stimulation on the sciatic nerve induced c-Fos expression in neurons of the spinal cord and celiac ganglion (CG). Then, the vagotomy reduced c-Fos levels in CG neurons but not in the spinal cord in animals given EA. Expression of $TNF-{\alpha}$ mRNA which was induced in the spleen after LPS was significantly inhibited by EA, then the vagotomy elevated $TNF-{\alpha}$ mRNA level similar to that in LPS-injected animals. Splanchnectomy in animals given LPS and EA also increased $TNF-{\alpha}$ mRNA though it was less effective than vagotomy. Conclusions : Our data suggest that EA delivered to the spleen via the splanchnic sympathetic nerve may be involved in attenuating splenic inflammatory responses in LPS-injected animals.

• Journal of Periodontal and Implant Science
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• 제52권1호
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• pp.28-38
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• 2022

Purpose: Macrophages play crucial roles as early responders to bacterial pathogens and promote/ or impede chronic inflammation in various tissues. Periodontal macrophage-induced pyroptosis results in physiological and pathological inflammatory responses. The transcription factor Dec2 is involved in regulating immune function and inflammatory processes. To characterize the potential unknown role of Dec2 in the innate immune system, we sought to elucidate the mechanism that may alleviate macrophage pyroptosis in periodontal inflammation. Methods: Porphyromonas gingivalis lipopolysaccharide (LPS) was used to induce pyroptosis in RAW 264.7 macrophages. Subsequently, we established an LPS-stimulated Dec2 overexpression cellular model in macrophages. Human chronic periodontitis tissues were employed to evaluate potential changes in inflammatory marker expression and pyroptosis. Finally, the effects of Dec2 deficiency on inflammation and pyroptosis were characterized in a P. gingivalis-treated experimental periodontitis Dec2-knockout mouse model. Results: Macrophages treated with LPS revealed significantly increased messenger RNA expression levels of Dec2 and interleukin (IL)-1β. Dec2 overexpression reduced IL-1β expression in macrophages treated with LPS. Overexpression of Dec2 also repressed the cleavage of gasdermin D (GSDMD), and the expression of caspase-11 was concurrently reduced in macrophages treated with LPS. Human chronic periodontitis tissues showed significantly higher gingival inflammation and pyroptosis-related protein expression than non-periodontitis tissues. In vivo, P. gingivalis-challenged mice exhibited a significant augmentation of F4/80, tumor necrosis factor-α, and IL-1β. Dec2 deficiency markedly induced GSDMD expression in the periodontal ligament of P. gingivalis-challenged mice. Conclusions: Our findings indicate that Dec2 deficiency exacerbated P. gingivalis LPS-induced periodontal inflammation and GSDMD-mediated pyroptosis. Collectively, our results present novel insights into the molecular functions of macrophage pyroptosis and document an unforeseen role of Dec2 in pyroptosis.

• 약학회지
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• 제45권6호
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• pp.715-723
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• 2001

Indomethacin is well known as a prostaglandin (PG) E$_2$ synthetase inhibitor which has antipyretic and anti-inflammatory effects and reduces the risk of cancer Growing tumors greatly induce hypersensitive responses to lipopolysaccharide (LPS). Thus, this study was investigated the effect of indomethacin on the LPS-induced production of cytokines in sarcoma-bearing ICR mice. Indomethacin at doses of 5mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$, levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the LPS-increased levels of IL-1$\beta$, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and interferon (IFN)-${\gamma}$ levels in supernatants, whereas indomethacin did not affect the LPS-increased levels of IL-2 and IFN-${\gamma}$. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1$\beta$, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-increased production of IL- 2 and IFN-${\gamma}$ in tumor-bearing state.