• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.427-438
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• 2022

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.2
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• pp.154-159
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• 2006

Interleukin-18 (IL-18), otherwise known as interferon-gamma-inducing factor (IGIF), is one of several well characterized and important cytokines that contribute to host defenses. The complementary DNA (cDNA) of mature human interleukin-18 gene (hIL-18) was fused with the signal peptide of the rice amylase 1A gene (Ramy1A) and introduced into the plant expression vector under the control of a duplicated CaMV 35S promoter. The recombinant plasmid was transformed into tobacco (Nicotiana tabacum L. cv Havana) using the Agrobacterium-mediated transformation method. The integration of the hlL-18 gene into the genome of transgenic tobacco plants was confirmed by polymerase chain reaction (PCR) amplification and its expression was observed in the suspension cells that were derived from the transgenic plant callus by using Northern blot analysis. The hlL-18 protein was detected in the extracts of the transgenic callus and in the medium of the transgenic tobacco suspension culture by using immunoblot analysis. Based upon enzyme-linked immunosorbant assay (ELISA) results, the expression level of the hlL-18 protein approximated $166{\mu}g/L$ in the suspension culture medium. Bioassay results from the induction of $interferon-{\gamma}$ from a KG-1 cell line indicated that the hlL-18 secreted into the suspension culture medium was bioactive.

• Vacuum Magazine
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• v.5 no.1
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• pp.18-22
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• 2018

• 대한두경부종양학회:학술대회논문집
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• 1986.11a
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• pp.18.1-18.1
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• 1986

• 대한두경부종양학회:학술대회논문집
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• 1994.11a
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• pp.18.1-18.1
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• 1994

• The Korean Publising Journal, Monthly
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• s.210
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• pp.18-18
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• 1997

• Korean Medical Education Review
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• v.18 no.3
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• pp.180-181
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• 2016

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1084-1098
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• 2023

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS: The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1832-1842
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• 2004

The present study was performed to examine the possible anti-inflammatory effects of a herbal drug ASCH in RAW264.7 cell line. Inflammation was induced by LPS toxin treatment to RAW264.7 macrophage cell line. Increases in cytokine production such as IL-1β, IL-6. and IL-18, COX-2, NOS-Ⅱ (iNOS), and TNF-alpha were observed at mRNA level in the LPS-treated RAW264.7 cells. Measurement of IL-6, nitric oxide and the reactive oxygen species (ROS) showed increased production of these inflammation mediators. Treatment of ASCH effectively decreased IL-1β protein in a dose-dependent manner, and IL-6 and IL-18 were reduced at 100㎍/㎖ of ASCH concentration. NO production was also decreased by ASCH treatment. A slight inhibition for TNF-alpha in terms of protein, but not mRNA level was obtained by 100㎍/㎖ of ASCH treatment. ASCH treatment to normal RAW264.7 cells did not produce any cytotoxicity, indicting that the action of ASCH was selective to inflammatory cells. Thus, the present data suggest that ASCH may act as an important regulator to alleviate the inflammatory symptoms.

• The Korea Journal of Herbology
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• v.31 no.6
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• pp.73-81
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• 2016

Objectives : $18{\beta}$-Glycyrrhetinic acid (18betaGA) is an metabolite of glycyrrhizin in Glycyrrhiza (licorice). The present study investigated anti-inflammatory and anti-apoptosis effect of 18betaGA on the brain tissue of lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : 18betaGA was administered orally with low (30 mg/kg) and high (100 mg/kg) doses for 3 days prior to LPS (3 mg/kg) injection. Pro-inflammatory cytokines mRNA including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, IL-6, and inflammatory enzyme cyclooxygenase-2 (COX-2) mRNA were measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Histological changes of Cornu ammonis area 1 (CA1) neurons, Bax, Bcl-2, and caspase-3 expression in the hippocampus was also evaluated by immunohistochemistry and Western blotting method. Results : 18betaGA significantly attenuated the up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 mRNA, and COX-2 mRNA expression in the brain tissues induced by the LPS injection. 18betaGA also significantly attenuated the reductions of the thickness of CA1 and the number of CA1 neurons. The up-regulation of Bax protein expression in the hippocampal tissue by the LPS injection was significantly attenuated, while the ratio of Bcl-2/Bax expression was increased by 18betaGA treatment. 18betaGA also significantly attenuated the up-regulation of Bax and caspase-3 expression in the CA1 of the hippocampus. Conclusion : This results indicate that 18betaGA has anti-inflammatory and anti-apoptosis effect under neuroinflammation induced by the LPS injection and suggest that 18betaGA may be a beneficial drug for various brain diseases accompanied with the brain tissue inflammation.