http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
A new era of macrophage-based cell therapy
Na Yi Rang,Kim Sang Wha,Seok Seung Hyeok 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Macrophages are essential innate immune cells found throughout the body that have protective and pathogenic functions in many diseases. When activated, macrophages can mediate the phagocytosis of dangerous cells or materials and participate in effective tissue regeneration by providing growth factors and anti-inflammatory molecules. Ex vivo-generated macrophages have thus been used in clinical trials as cell-based therapies, and based on their intrinsic characteristics, they outperformed stem cells within specific target diseases. In addition to the old methods of generating naïve or M2 primed macrophages, the recently developed chimeric antigen receptor-macrophages revealed the potential of genetically engineered macrophages for cell therapy. Here, we review the current developmental status of macrophage-based cell therapy. The findings of important clinical and preclinical trials are updated, and patent status is investigated. Additionally, we discuss the limitations and future directions of macrophage-based cell therapy, which will help broaden the potential utility and clinical applications of macrophages.
Kim, MinJeong,Gu, Gyo Jeong,Koh, Yun-Sook,Lee, Su-Hyun,Na, Yi Rang,Seok, Seung Hyeok,Lim, Kyung-Min The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.6
Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration-(>$50{\mu}M$) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to $500{\mu}M$. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at$25{\mu}M$. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.
Na, Yi Rang,Hong, Ji Hye,Lee, Min Yong,Jung, Jae Hun,Jung, Daun,Kim, Young Won,Son, Dain,Choi, Murim,Kim, Kwang Pyo,Seok II, Seung Hyeok The American Society for Biochemistry and Molecula 2015 Molecular and Cellular Proteomics Vol.14 No.10
<P>Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs up-regulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs.</P>
Kim, So Won,Hasanuzzaman, Md.,Cho, Munju,Heo, Ye Rang,Ryu, Min-Jung,Ha, Na-Young,Park, Hyun June,Park, Hyung-Yeon,Shin, Jae-Gook American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.27
<P>The P-glycoprotein (P-gp) encoded by the MDR1 gene is a drug-exporting transporter located in the cellular membrane. P-gp induction is regarded as one of the main mechanisms underlying drug-induced resistance. Although there is great interest in the regulation of P-gp expression, little is known about its underlying regulatory mechanisms. In this study, we demonstrate that casein kinase 2 (CK2)-mediated phosphorylation of heat shock protein 90 beta (Hsp90 beta) and subsequent stabilization of PXR is a key mechanism in the regulation of MDR1 expression. Furthermore, we show that CK2 is directly activated by rifampin. Upon exposure to rifampin, CK2 catalyzes the phosphorylation of Hsp90 beta at the Ser-225/254 residues. Phosphorylated Hsp90 beta then interacts with PXR, causing a subsequent increase in its stability, leading to the induction of P-gp expression. In addition, inhibition of CK2 and Hsp90 beta enhances the down-regulation of PXR and P-gp expression. The results of this study may facilitate the development of new strategies to prevent multidrug resistance and provide a plausible mechanism for acquired drug resistance by CK2-mediated regulation of P-gp expression.</P>
GM-CSF Induces Inflammatory Macrophages by Regulating Glycolysis and Lipid Metabolism
Na, Yi Rang,Gu, Gyo Jung,Jung, Daun,Kim, Young Won,Na, Juri,Woo, Jin Sun,Cho, Joo Youn,Youn, Hyewon,Seok, Seung Hyeok The American Association of Immunologists, Inc. 2016 JOURNAL OF IMMUNOLOGY Vol.197 No.10
<P>GM-CSF induces proinflammatory macrophages, but the underlying mechanisms have not been studied thus far. In this study, we investigated the mechanisms of how GM-CSF induces inflammatory macrophages. First, we observed that GM-CSF increased the extent of LPS-induced acute glycolysis in murine bone marrow-derived macrophages. This directly correlates with an inflammatory phenotype because glycolysis inhibition by 2-deoxyglucose abolished GM-CSF-mediated increase of TNF-alpha,IL-1 beta, IL-6, and IL-12p70 synthesis upon LPS stimulation. Increased glycolytic capacity is due to de novo synthesis of glucose transporter ( GLUT)-1,-3, and-4, as well as c-myc. Mean while, GM-CSF increased 3-hydroxy-3-methyl-glutaryl-CoA reductase, which is the rate-limiting enzyme of the mevalonate pathway. Inhibition of acute glycolysis or 3-hydroxy-3-methyl-glutaryl-CoA reductase abrogated the inflammatory effects of GM-CSF priming in macrophages. Finally, mice with inflamed colons exposed to dextran sodium sulfate containing GLUT-1(high) macrophages led to massive uptake of [F-18]-fluorodeoxyglucose, but GM-CSF neutralization reduced the positron-emission tomography signal in the intestine and also decreased GLUT-1 expression in colonic macrophages. Collectively, our results reveal glycolysis and lipid metabolism created by GM-CSF as the underlying metabolic constructs for the function of inflammatory macrophages.</P>
Production of Syngas from Oxygen Gasification of Industrial Solid Waste in a Fixed-bed Reactor
( Na-rang Kim ),( Soo-nam Park ),( Jae-hong Min ),( Jae-hoi Gu ),( Sang-ok Choi ),( In-su Lee ),( Soo-tae Choo ) 한국폐기물자원순환학회(구 한국폐기물학회) 2015 한국폐기물자원순환학회 3RINCs초록집 Vol.2015 No.-
Waste gasification technologies are currently proposed as an alternative to conventional Waste-to-Energy plants. Important objective of waste gasification is to convert this solid resource into combustible clean gas at high efficiency. The experiment of the gasification was conducted using a pilot scale waste gasification process. The effect of gasification temperatures on syngas composition, cold gas efficiency and particulate concentration were investigates. The final gasification temperature used ranged from 751~1,188 ℃. The highest CO+H<sub>2</sub> composition of 85.5% and CGE of 67.8% and the lowest particulate concentration of 8,803 mg/Nm<sup>3</sup> were obtained at final gasification temperature of 1,188℃.
Na, Yi-Rang,Seok, Seung-Hyeok,Kim, Dong-Jae,Han, Ju-Hee,Kim, Tae-Hyoun,Jung, Hyun,Lee, Byoung-Hee,Park, Jae-Hak Wiley (Blackwell Publishing) 2009 Cancer Science Vol.100 No.11
<P>Bone morphogenetic protein (BMP) 7 counteracts physiological epithelial-to-mesenchymal transition, a process that is indicative of epithelial plasticity in developmental stages. Because epithelial-to-mesenchymal transition and its reversed process mesenchymal-to-epithelial transition (MET) are also involved in cancer progression, we investigated whether BMP7 plays a role in WM-266-4 melanoma cell growth and metastasis. An MTT assay was conducted in WM-266-4 and HEK293T cell lines to show the cell growth inhibition ability of BMP7 and cisplatin. Semiquantitative RT-PCR was used to determine MET in morphologically changed BMP7-treated melanoma cells. MET-induced cells expressed less a basic helix-loop-helix transcription factor (TWIST) in western blot analysis, and we confirm that BMP receptor (Alk2) siRNA transduction could restore TWIST protein expression via blocking of Smad 1, 5 and 8 signaling. Matrigel invasion and cell migration assays were done to investigate the BMP7-induced metastasis inhibition ability. BMP7 treatment only slightly reduced cell growth rate, but induced apparent MET. BMP7 also reduced the invasion and migration ability. Furthermore, BMP7 reduced the resistance of WM-266-4 cells to cisplatin. Collectively, our findings indicate that the metastatis inhibition ability of BMP7 is involved in MET, and that BMP7 could be used as a potential metastasis inhibitor in human melanoma cells.</P>