• Title/Summary/Keyword: M1 polarization

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S1P1 Regulates M1/M2 Polarization toward Brain Injury after Transient Focal Cerebral Ischemia

  • Gaire, Bhakta Prasad;Bae, Young Joo;Choi, Ji Woong
    • Biomolecules & Therapeutics
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    • v.27 no.6
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    • pp.522-529
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    • 2019
  • M1/M2 polarization of immune cells including microglia has been well characterized. It mediates detrimental or beneficial roles in neuroinflammatory disorders including cerebral ischemia. We have previously found that sphingosine 1-phospate receptor subtype 1 ($S1P_1$) in post-ischemic brain following transient middle cerebral artery occlusion (tMCAO) can trigger microglial activation, leading to brain damage. Although the link between $S1P_1$ and microglial activation as a pathogenesis in cerebral ischemia had been clearly demonstrated, whether the pathogenic role of $S1P_1$ is associated with its regulation of M1/M2 polarization remains unclear. Thus, this study aimed to determine whether $S1P_1$ was associated with regulation of M1/M2 polarization in post-ischemic brain. Suppressing $S1P_1$ activity with its functional antagonist, AUY954 (5 mg/kg, p.o.), attenuated mRNA upregulation of M1 polarization markers in post-ischemic brain at 1 day and 3 days after tMCAO challenge. Similarly, suppressing $S1P_1$ activity with AUY954 administration inhibited M1-polarizatioin-relevant $NF-{\kappa}B$ activation in post-ischemic brain. Particularly, $NF-{\kappa}B$ activation was observed in activated microglia of post-ischemic brain and markedly attenuated by AUY954, indicating that M1 polarization through $S1P_1$ in post-ischemic brain mainly occurred in activated microglia. Suppressing $S1P_1$ activity with AUY954 also increased mRNA expression levels of M2 polarization markers in post-ischemic brain, further indicating that $S1P_1$ could also influence M2 polarization in post-ischemic brain. Finally, suppressing $S1P_1$ activity decreased phosphorylation of M1-relevant ERK1/2, p38, and JNK MAPKs, but increased phosphorylation of M2-relevant Akt, all of which were downstream pathways following $S1P_1$ activation. Overall, these results revealed $S1P_1$-regulated M1/M2 polarization toward brain damage as a pathogenesis of cerebral ischemia.

Paeonol accelerates skin wound healing by regulating macrophage polarization and inflammation in diabetic rats

  • Zuyang Zhang;Tianhua Chen;Wei Liu;Jiepeng Xiong;Liangdong Jiang;Mingjiang Liu
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.5
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    • pp.437-448
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    • 2023
  • Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

Anti-migration Effects of the Daesiho-tang (Da Chai Hu-Tang) Water Extract in Cancer Cells by Regulating Macrophage Polarization (대식세포 분화 조절을 통한 대시호탕의 암세포 전이 억제 효과)

  • Jae-Hoon Jeong;Shin-Hyung Park
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.38 no.1
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    • pp.32-37
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    • 2024
  • The aim of this study was to investigate the role of Daesiho-tang (Da Chai Hu-Tang) water extract (DSTE) in regulating chronic stress-induced cancer progression, focusing on its activity in modulating tumor-associated macrophages (TAMs). Different stimuli can polarize TAMs into immune-stimulating M1 macrophages or immunosuppressive M2 macrophages. During cancer progression, M2 phenotype increases and supports tumor growth, angiogenesis and metastasis. Notably, chronic stress-induced catecholamines promote M2 macrophage polarization. In this study, we investigated whether DSTE regulates norepinephrine (NE)-induced M2 macrophage polarization in RAW 264.7 mouse macrophage cells. Even though NE itself did not increase the expression of M2 markers, the conditioned media of NE-treated 4T1 mouse breast cancer cells (NE CM) significantly up-regulated M2 markers in RAW 264.7 cells, suggesting that NE-regulated cancer cell secretome stimulated M2 polarization. However, such increase was abrogated by DSTE. NE CM also induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) in RAW 264.7 cells, which was clearly reversed by pretreatment with DSTE, demonstrating that DSTE inhibited M2 polarization by inactivating STAT6. Finally, M2-polarized RAW264.7 cells by NE CM markedly increased the migration of 4T1 cells. However, such increase was completely reversed by co-treating RAW264.7 cells with NE CM and DSTE, indicating that DSTE attenuated cancer cell migration by blocking M2 polarization. Taken together, our results suggest a probable use of DSTE for cancer patients under chronic stress by regulating M2 macrophage polarization.

Polarization of THP-1-Derived Macrophage by Magnesium and MAGT1 Inhibition in Wound Healing

  • Mun Ho Oh;JaeHyuk Jang;Jong Hun Lee
    • Archives of Plastic Surgery
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    • v.50 no.4
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    • pp.432-442
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    • 2023
  • Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.

Ethyl Acetate Fraction of Adenophora triphylla var. japonica Inhibits Migration of Lewis Lung Carcinoma Cells by Suppressing Macrophage Polarization toward an M2 Phenotype

  • Park, Shin-Hyung
    • Journal of Pharmacopuncture
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    • v.22 no.4
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    • pp.253-259
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    • 2019
  • Objectives: It is reported that tumor-associated macrophages (TAMs) contribute to cancer progression by promoting tumor growth and metastasis. The purpose of this study is to investigate the effect of different fractions of Adenophora triphylla var. japonica (AT) on the polarization of macrophages into the M2 phenotype, a major phenotype of TAMs. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AT. The cytotoxicity of AT in RAW264.7 cells was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RAW264.7 cells were polarized into the M2 phenotype by treatment with interleukin (IL)-4 and IL-13. The expression of M2 macrophage marker genes was detected by reverse transcription polymerase chain reaction (RT-PCR). The phosphorylation level of signal transducer and activator of transcription 6 (STAT6) was investigated by western blot analysis. The migration of Lewis lung carcinoma (LLC) cells was examined by transwell migration assay using conditioned media (CM) collected from RAW264.7 cells as a chemoattractant. Results: Among various fractions of AT, the ethyl acetate fraction of AT (EAT) showed the most significant suppressive effect on the mRNA expression of M2 macrophage markers, including arginase-1, interleukin (IL)-10 and mannose receptor C type 1 (MRC-1), up-regulated by treatment of IL-4 and IL-13. In addition, EAT suppressed the phosphorylation of STAT6, a critical regulator of IL-4 and IL-13-induced M2 macrophage polarization. Finally, the increased migration of Lewis lung carcinoma (LLC) cells by CM from M2-polarized RAW264.7 cells was reduced by CM from RAW264.7 cells co-treated with EAT and M2 polarization inducers. Conclusion: We demonstrated that EAT attenuated cancer cell migration through suppression of macrophage polarization toward the M2 phenotype. Additional preclinical or clinical researches are needed to evaluate its regulatory effects on macrophage polarization and anti-cancer activities.

Using the Crab Nebula as Polarization Angle Calibrator for the Korean VLBI Network

  • Minchul Kam;Sascha Trippe;Do-Young Byun;Jongho Park;Sincheol Kang;Naeun Shin;Sang-Sung Lee;Taehyun Jung
    • Journal of The Korean Astronomical Society
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    • v.56 no.1
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    • pp.1-9
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    • 2023
  • The Crab nebula is widely used as a polarization angle calibrator for single-dish radio observations because of its brightness, high degree of linear polarization, and well-known polarization angle over a wide frequency range. However, the Crab nebula cannot be directly used as a polarization angle calibrator for single-dish observations with the Korean VLBI Network (KVN), because the beam size of the telescopes is smaller than the size of the nebula. To determine the polarization angle of the Crab nebula as seen by KVN, we use 3C 286, a compact polarized extragalactic radio source whose polarization angle is well-known, as a reference target. We observed both the Crab nebula and 3C 286 with the KVN from 2017 to 2021 and find that the polarization angles at the total intensity peak of the Crab nebula (equatorial coordinates (J2000) R.A. = 05h34m32.3804s and Dec = 22°00'44.0982'') are 154.2° ± 0.3°, 151.0° ± 0.2°, 150.0° ± 1.0°, and 151.3° ± 1.1° at 22, 43, 86, and 94 GHz, respectively. We also find that the polarization angles at the pulsar position (RA = 05h34m31.971s and Dec = 22°00'52.06'') are 154.4° ±0.4°, 150.7° ±0.4°, and 149.0° ± 1.0° for the KVN at 22, 43, and 86 GHz. At 129 GHz, we suggest to use the values 149.0° ± 1.6° at the total intensity peak and 150.2° ± 2.0° at the pulsar position obtained with the Institute for Radio Astronomy in the Millimeter Range (IRAM) 30-meter Telescope. Based on our study, both positions within the Crab nebula can be used as polarization angle calibrators for the KVN single-dish observations.

Spin Polarization of CuD Nanowires

  • Hong, Ji-Sang
    • Journal of Magnetics
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    • v.11 no.1
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    • pp.20-24
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    • 2006
  • Very recently, it was presented that the one dimensional (1D) CuO atomic chains can maintain large magnetic moments. In this work, we analyzed m-resolved density of states (DOS) to understand the peculiar spin polarization occurred in Cu atoms. It was found that the $\mid{m}\mid=1$ states play an essential role in the spin polarization of Cu atoms. In addition, we calculated magnetic anisotropy energy (MAE) and observed that the distribution of MAE is strongly sensitive to the interatomic distance between Cu and O atoms. Besides, it was revealed that the contribution to MAE comes for the second half of Brillouin zone (BZ).

Solid State Dynamic Nuclear Polarization of 1H Nuclear Spins at 0.3 T and 4.2 K

  • Shim, Jeong Hyun
    • Journal of the Korean Magnetic Resonance Society
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    • v.21 no.4
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    • pp.114-118
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    • 2017
  • Here, I report solid state Dynamic Nuclear Polarization (DNP) of $^1H$ nuclear spins at 0.3 T and 4.2 K. The DNP polarizer was developed based on a commercial X-band Electron Spin Resonance (ESR) modified for DNP, in combination with a NMR console and a liquid-Helium cryostat. By detuning magnetic field, DNP spectrum was measured to find the optimal condition. At +3 mT detuned from on-resonance field, $^1H$ NMR signal of 60:40 glycerol/water frozen solution doped with 20 mM perdeuterated-Tempone was amplified 43 times. The $^1H$ spin polarization obtained at 4.2 K is over 3100 times higher than that at 300 K. The width of the DNP spectrum, which is five times broader than ESR spectrum, is inconsistent with solid effect or thermal mixing, and presumably suggests a different DNP mechanism.

Passive Polarization Converter Fabricated by Controlling Optic Axis of Poled Polymer Waveguides (폴링된 폴리머 광도파로의 광축을 조절하여 제작한 수동형 편광 변환기)

  • 오민철;신상영
    • Journal of the Korean Institute of Telematics and Electronics A
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    • v.32A no.12
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    • pp.166-172
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    • 1995
  • A novel passive TE/TM polarization mode converter is fabricated by using poled polymer waveguides. The optic axis of the poling induced waveguide is slowly rotated by using a slowly varying structure of poling electrodes. Thus the polarization conversion is achieved as the guided mode propagates through the waveguide. The proposed device is simulated by a full vectorial beam propagation method (VBPM) for anisotropic medium. For the rotation length of 1 mm, the TE polarization of the guided mode is successfully converted to the TM polarization with negligible loss. Based on the simulation results, we fabricated the polarization converter which is tested by using 1.3 $\mu$m laser diode. TE to TM mode conversion is observed with a polarization extinction ratio higher than 30 dB, and the excess loss is less than 1 dB. The polarization conversion is relatively insensitive to wavelength since the device contains no periodic structures. These devices are easier to fabricate than others containing periodic structures.

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Suppression of polarization effects in Er-doped fiber source for gyroscope by polarization scrambling (자이로용 Er-첨가 광섬유 광원에서 편광 스크램블링을 이용한 편광효과의 억제)

  • 김택중;진영준;박희갑
    • Korean Journal of Optics and Photonics
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    • v.14 no.4
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    • pp.449-453
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    • 2003
  • In a broadband erbium-doped fiber source for fiber optic gyroscope, a pump-polarization scrambling scheme is used to suppress the polarization dependence of the source mean wavelength. The degree of polarization of the pump is reduced to 1.4% by applying proper modulation depth to the polarization modulator where 10 m-long single-mode fiber is wound on a cylindrical PZT. In the case of using the pump-polarization scrambler as well as the output depolarizer, the mean-wavelength variations due to the random change of polarization are measured to be less than our measurement limit of 5 ppm.