• Title/Summary/Keyword: activated macrophage

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The role of macrophage in lipid accumulation

  • Ishii, Itsuko
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.37-43
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    • 2003
  • Engorgement of macrophages with cholesterol is the defining pathological characteristic of atherosclerotic plaques, the cause of most heart attacks and strokes. Activated human macrophages uptake low density lipoprotein (LDL) by the bulk-phase fluid, and aggregated LDL by patocytosis. After incorporation of LDL and aggregated LDL into macrophages, neutral cholesterol esterase is decreased and cholesterol efflux is also deceased, resulting that macrophages become foam cells.

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Regulation of $Ca^{2+}$ Influx by Membrane Potential in Microglia

  • Lee, Jungsun;Uhm, Dae-Yong;Sungkwon Chung
    • Proceedings of the Korean Biophysical Society Conference
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    • 2002.06b
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    • pp.39-39
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    • 2002
  • Microglia are known to have an important function as brain macrophage during immunological processes, oncogenesis, and regeneration in the central nervous system (CNS). A wide variety of ion channels have been identified and characterized in microglia including inward rectifier $K^{+}$ channel (Kir), voltage dependent $K^{+}$ channel (Kv), $Ca^{2+}$-release activated $Ca^{2+}$ channel (CRAC).(omitted)

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Inhibitors of Nitric Oxide Synthesis from Ginseng in Activated Macrophages (활성화한 RAW 264.7 세 포주에서 인삼 Polyacetylene류의 Nitric Oxide 생성저해)

  • 류재하;장세란
    • Journal of Ginseng Research
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    • v.22 no.3
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    • pp.181-187
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    • 1998
  • Nitric Oxide (NO), derived from L-arginine, is produced by two types (constitutive and inducible) of nitric oxide synthase (NOS). The NO produced in large amounts by the inducible NOS is known to be responsible for the vasodilation and hypotension observed in septic shock. We have found three polyacetylene compounds which inhibited the production of NO in LPS-activated RAW 264.7 cells. Their structures were identified as panauynol, ginsenoyne A and PQ-6 by the spec- troscopic analysis (IC50 values were 32.3 $\mu$M, 2.3 $\mu$M, 1.5 $\mu$M, respectively). These polyacetylenes may be useful candidates for the development of new drug to treat endotoxemia and inflammation accompanied by the overproduction of NO.

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p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Regulated Kinase Regulate Nitric Oxide Production and Inflammatory Cytokine Expression in Raw Cells

  • Choi, Cheol-Hee;Kim, Sang-Hyun
    • IMMUNE NETWORK
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    • v.5 no.1
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    • pp.30-35
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    • 2005
  • Background: p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling are thought to have critical role in lipopolysaccharide (LPS)-induced immune response but the molecular mechanism underlying the induction of these signaling are not clear. Methods: Specific inhibitors for p38, SB203580, and for ERK, PD98059 were used. Cells were stimulated by LPS with or without specific MAPK inhibitors. Results: LPS activated inducible nitric oxide synthase (iNOS), subsequent NO productions, and pro-inflammatory cytokine gene expressions (TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and IL-12). Treatment of both SB203580 and PD98059 decreased LPS-induced NO productions. Concomitant decreases in the expression of iNOS mRNA and protein were detected. SB203580 and PD98059 decreased LPS-induced gene expression of IL-$1{\beta}$ and IL-6. SB203580 increased LPS-induced expression of TNF-${\alpha}$ and IL-12, and reactive oxygen species production, but PD98059 had no effect. Conclusion: These results indicate that both p38 and ERK pathways are involved in LPS-stimulated NO synthesis, and expression of IL-$1{\beta}$ and IL-6. p38 signaling pathways are involved in LPS-induced TNF-${\alpha}$ and IL-12, and reactive oxygen species plays an important role in these signaling in macrophage.

A Role of Mitogen Activated Protein Kinases and Inflammatory Responses in Gender Differences in Kidney Ischemia Injury

  • Park, Kwon-Moo;Han, Ho-Jae
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.3
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    • pp.155-160
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    • 2002
  • It is not known whether gender differences play a role in susceptibility to ischemic acute renal failure. Thus, we examined if there were any differences in susceptibility between male and female mice to kidney ischemic injury, and if so, whether it is due to differences in mitogen activated protein kinases (MAPKs) or inflammatory responses to ischemia. Female mice were protected against kidney ischemia when compared with males. Thirty minutes of bilateral ischemia resulted in marked functional and morphological damages in males, but not in females. The ischemia-induced phosphorylation of c-jun N-terminal stress-activated protein kinases (JNKs) was higher in males than in females. Phosphorylation of extracellular signal-regulated kinases (ERKs) was lower in males than in females. Post- ischemia medullary infiltration of RAW 264.7 cell, a monocyte-macrophage cell, and intercellular adhesion molecule-1 (ICAM-1) were greater in males than in females. In conclusion, males were much more susceptible to ischemia than females. The enhanced propensity to ischemic injury in males was correlated with greater activation of JNKs, greater expression of ICAM-1, and greater trapping of leukocytes in the medulla.

Inhibitory Activity of Chinese Medicinal Plants on Nitric Oxide Synthesis in Lipopolysaccharide -Activated Macrophages

  • Ryu, Jae-Ha;Ahn, Han-Na;Lee, Hwa-Jin;Feng, Li;Qun, Wen-He;Han, Yong-Nam;Han, Byung-Hoon
    • Biomolecules & Therapeutics
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    • v.9 no.3
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    • pp.183-187
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    • 2001
  • Nitric oxide (NO) produced in large amounts by the inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. The inhibitors of iNOS, thus, may be useful candidate for the treatment of inflammatory diseases accompanied by the overproduction of NO. We prepared alcoholic extracts of Chinese medicinal plants and screened their inhibitory activity against NO production in lipopolysaccharide (LPS)-activated macrophages. Among the 80 kinds of extracts of herbal drugs, 15 extracts showed potent inhibitory activity of NO production above 80% at the concentration o$50\mu\textrm{g}/ml$. These potent extracts showed dose dependent inhibition of NO production of LPS-activated macrophages at the concentration of 50, 30,$10\mu\textrm{g}/ml$. Especially, Rhus chinensis, Senecio scandens and Wikstroemia indica showed most potent inhibition above 50% at the concentration of $10\mu\textrm{g}/ml$. These plants are promising candidates for the study of the activity-guided purification of active compounds and would be useful for the treatment of inflammatory diseases and endotoxemia accompanying the overproduction of NO.

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Cell Surface Expression of Tumor Necrosis Factor-Alpha by Activated Rat Astrocytes

  • Chung, Il-Yup;Benveniste, Etty N.
    • BMB Reports
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    • v.29 no.6
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    • pp.530-534
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    • 1996
  • Astrocyte are the major glial cell type in the central nervous system (CNS), and analogous to macrophage, mediates the number of immune responses such as production of cytokines including tumor necrosis factor alpha ($TNF-{\alpha}$) upon activation. $TNF-{\alpha}$ has been implicated in neuroimmunological disorders through killing oligodendrocytes and thus causing demyelination. It has been previously demonstrated that mitogen-activated T cells synthesized a 26 kDa precursor form of $TNF-{\alpha}$ which is bound to the surface of a membrane, and is later secreted as a 17 kDa mature version. In order to examine whether astrocytes would produce the transmembrane form of $TNF-{\alpha}$, astrocytes were stimulated with biological stimuli and the membrane form of $TNF-{\alpha}$ was analyzed by Western blot and FACS analysis. When astrocytes are stimulated with lipopolysaccharide (LPS), $IFN-{\gamma}/LPS$, or $IFN-{\gamma}/IL-1{\beta}$, they were able to express a membrane-anchored $TNF-{\alpha}$ of approximately 26 kDa protein which was immunoreactive to an $anti-TNF-{\alpha}$ antibody, whereas unstimulated astrocytes or astrocytes treated with $IFN-{\gamma}$ or $IL-1{\beta}$ alone was not. Our FACS data were also consistent with the immunoblot analysis. Our result suggests that the membrane form of $TNF-{\alpha}$ expressed by activated astrocytes may cause local damage to oligodendrocytes by direct cell-cell contact and contribute to demyelination observed in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE).

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Canavalia gladiata regulates the immune responses of macrophages differently depending on the extraction method

  • Lee, Ha-Nul;Kim, Young-Min;Jang, Ah-Ra;Kim, Young Ran;Park, Jong-Hwan
    • Korean Journal of Food Science and Technology
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    • v.52 no.6
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    • pp.622-626
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    • 2020
  • Recent studies have suggested that Canavalia gladiate, a dietary food and traditional folk medicine, has promising pharmaceutical potential, but the effects have mostly been demonstrated using its organo-soluble extract. To date, its immunomodulatory effect depending on the extraction method is unclear. Here, the immune responses of macrophages to C. gladiate and the underlying mechanisms were studied. C. gladiate hot water extract (CGW) induced cytokine production in bone marrow-derived macrophages (BMDMs) in a dose-dependent manner, whereas its ethanolic extract (CGE) did not. Immunoblotting analysis also showed that CGW activated nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs). Moreover, an inhibitor assay revealed the involvement of NF-κB, p38, and JNK, but not ERK, in CGW-induced cytokine production. CGE inhibited lipopolysaccharide-stimulated production of pro-inflammatory cytokines and activation of NF-κB and MAPKs in BMDMs. The results suggest that C. gladiate regulates the immune responses of macrophages differently depending on the extraction method.