• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.346-351
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• 2012

Cells show various stress signs when they are challenged with severe physiological problems. Majority of such cellular stresses are conveyed to endoplasmic reticulum (ER) and unfolded protein response (UPR) serves as typical defense mechanism against ER stress. This study investigated an interaction between ER stress agents using macropage cell line Raw 264.7. When activated by lipopolysaccharide (LPS), the cell lines showed typical indicators of ER stress. Along with molecular chaperones, the activation process leads to the production of additional inflammatory mediators. Following activation, the macrophage cell line was further treated with TUN and characterized in terms of chaperone expression and cytokine secretion. When treated with TUN, the activated macrophage cell leads to increased secretion of IL-6 although expression of ER stress markers, GRP94 and GRP78 increased. The secretion of cytokines continued until the addition of BFA which inhibits protein targeting from ER to Golgi. However, secretion of cytokines was ceased upon dual treatments with BFA and TG. This result strongly implies that cells may differently deal with various polypeptides depending on the urgency in cellular function under ER stress. Considering IL-6 is one of the most important signal molecules in macrophage, the molecule might be able to circumvent ER stress and UPR to reach its targeting site.

• Journal of Ginseng Research
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• v.14 no.3
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• pp.364-372
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• 1990

This experiment was performed to investigate the effects of ginseng saponin fractions (total saponin, triol saponin. diol saponin) and lipopolysacrharide (LPS) on the tllmoricidal activity of macrophage. The ginseng saponin fractions had little effect on the tumoricidal activity of macrophage (less than 10%). When the ginseng saponin fractions were treated with LPS, the effects of tumoricidal activation of macrophage increased a relatively high percent, and the total saponin and triol saponin (20-35%) were ulore effectual than diol saponin (15-25%). The effects of ginseng saponin and LPS on the tumoricidal activity of macrophage were mediated by the induction of macrophage-release factor(5) which has(have) the capacity of tumor cell killing. And the quantity of the (actors) was(were) increased by the contact of macrophage with tumor cell.

• Applied Biological Chemistry
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• v.48 no.3
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• pp.246-251
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• 2005

The aim of this study was to evaluate an efficacy about activation on macrophage, using model that measured cell viability, nitric oxide (NO), iNOS (inducible nitric oxide synthase) expression and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) on Raw 264.7 cells following treatment of Germanium-fortified Yeast in 0, 5, 10, 25, 50, 100, $200\;{\mu}g/ml$ and the same concentration of dried yeast without germanium. Cell viability (%) and NO produced in activated-macrophage were dose-dependant, a significant increase of the cell viability (132.5%) and NO in $10\;{\mu}g/ml$ (p < 0.05). Increase in iNOS level was in $10\;{\mu}g/ml$. $TNF-{\alpha}$ was produced dose-dependant, e.g. in activated-macrophage with a significant increase of the $TNF-{\alpha}$ in 5 and $10\;{\mu}g/ml$ (p < 0.05). Therefore, Germanium-fortified Yeast had an efficacy of NO mediated iNOS and $TNF-{\alpha}$ production by activated macrophage. This result showed that Germanium-fortified Yeast induced activation of cellular immunity, returned to normalcy on injured immune system and procured anticancer system by activation of macrophage, which was important in immune and anticancer function.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.245-252
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• 2020

Macrophage cell death contributes to the formation of plaque, leading to the development of atherosclerosis. The accumulation of triglyceride (TG) is also associated with the pathogenesis of atherosclerosis. A previous study reported that TG induces the cell death of macrophages. This study examined whether the cytoplasmic release of cathepsin B from lysosome is associated with the TG-induced cell death of macrophage. The release of cathepsin B was increased in the TG-treated THP-1 macrophages, but the TG treatment did not affect cathepsin B expression. Furthermore, the inhibition of cathepsin B by its inhibitor, CA-074 Me, partially inhibited the TG-induced cell death of macrophage. TG-triggered macrophage cell death is mediated by the activation of caspase-1, -2, and apoptotic caspases. Therefore, this study investigated whether cathepsin B is implicated in the activation of these caspases. The inhibition of cathepsin B blocked the activation of caspase-7, -8, and -1 but did not affect the activity of caspase-3, -9, and -2. Overall, these results suggest that TG-induced cytoplasmic cathepsin B causes THP-1 macrophage cell death by activating caspase-1, leading to subsequent activation of the extrinsic apoptotic pathway.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.26-30
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• 2007

Background: Mycobacterial antigens released as PIM, LM, LAM, lipoproteins and other cellular factors may contribute to macrophage and dendritic cell activation through pattern recognition receptors such as TLRs. In this study, we assessed cytokine production and ERK activation with stimulation of several major mycobacterial antigens. Methods: Purified mycobacterial antigens (10, 22, 30, 38kDa) and recombinant antigens (6, 16, 19, 38kDa, Ag85A antigen) were studied. The production of cytokines (TNF-${\alpha}$, IL-12, IL-6) was measured by ELISA. The ERK activation was detected by western blotting. The expression of TLR2 or TLR4 was measured by flow cytometry. Results: Among purified antigens only 30kDa antigen induced production of IL-6 or TNF-${\alpha}$ in THP-1 macrophage cells. When THP-1 macrophage cells were treated with 30kDa antigen, phosphorylation of ERK was detected. ERK activation also occurred in TLR2 transfectant HEK293 cells with 30kDa antigen stimulation. Conclusion: 30kDa antigen is one of the major mycobacterial antigens inducing cytokine production and MAP kinases phosphorylation in macrophages.

• IMMUNE NETWORK
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• v.10 no.5
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• pp.173-180
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• 2010

Background: APRIL, originally known as a cytokine involved in B cell survival, is now known to regulate the inflammatory activation of macrophages. Although the signal initiated from APRIL has been demonstrated, its role in cellular activation is still not clear due to the presence of BAFF, a closely related member of TNF superfamily, which share same receptors (TACI and BCMA) with APRIL. Methods: Through transfection of siRNA, BAFF-deficient THP-1 cells (human macrophage-like cells) were generated and APRIL-mediated inflammatory activities were tested. The expression patterns of APRIL were also tested in vivo. Results: BAFF-deficient THP-1 cells responded to APRIL-stimulating agents such as monoclonal antibody against APRIL and soluble form of TACI or BCMA. Furthermore, co-incubation of the siBAFF-deficient THP-1 cells with a human B cell line (Ramos) resulted in an activation of THP-1 cells which was dependent on interactions between APRIL and TACI/BCMA. Immunohistochemical analysis of human pathologic samples detected the expression of both APRIL and TACI in macrophage-rich areas. Additionally, human macrophage primary culture expressed APRIL on the cell surface. Conclusion: These observations indicate that APRIL, which is expressed on macrophages in pathologic tissues with chronic inflammation, may mediate activation signals through its interaction with its counterparts via cell-to-cell interaction.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.341-348
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• 2024

Endoplasmic reticulum (ER) stress plays a crucial role in liver diseases, affecting various types of hepatic cells. While studies have focused on the link between ER stress and hepatocytes as well as hepatic stellate cells (HSCs), the precise involvement of hepatic macrophages in ER stress-induced liver injury remains poorly understood. Here, we examined the effects of ER stress on hepatic macrophages and their role in liver injury. Acute ER stress led to the accumulation and activation of hepatic macrophages, which preceded hepatocyte apoptosis. Notably, macrophage depletion mitigated liver injury induced by ER stress, underscoring their detrimental role. Mechanistic studies revealed that ER stress stimulates macrophages predominantly via the PERK signaling pathway, regardless of its canonical substrate ATF4. hnRNPA1 has been identified as a crucial mediator of PERK-driven macrophage activation, as the overexpression of hnRNPA1 effectively reduced ER stress and suppressed pro-inflammatory activation. We observed that hnRNPA1 interacts with mRNAs that encode UPR-related proteins, indicating its role in the regulation of ER stress response in macrophages. These findings illuminate the cell type-specific responses to ER stress and the significance of hepatic macrophages in ER stress-induced liver injury. Collectively, the PERK-hnRNPA1 axis has been discovered as a molecular mechanism for macrophage activation, presenting prospective therapeutic targets for inflammatory hepatic diseases such as acute liver injury.

• Biomedical Science Letters
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• v.18 no.4
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• pp.345-354
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• 2012

Angelica keiskei has exhibited numerous pharmacological effects including antitumor, antimetastatic, and antidiabetic effects. However, the anti-inflammatory effects and mechanisms employed by xanthoangelol E isolated from Angelica keiskei are incompletely understood. In this study, we attempted to determine the effects of Xanthoangelol E on the lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophage. The findings of this study demonstrated that xanthoangelol E inhibited the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and prostaglandin $E_2$ ($PGE_2$). Xanthoangelol E inhibited the enhanced levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) caused by LPS. Additionally, we showed that the anti-inflammatory effect of xanthoangelol E is through the regulation of the activation of nuclear factor (NF)-${\kappa}B$ and caspase-1. These results provide novel insights into the pharmacological actions of xanthoangelol E as a potential candidate for the development of new drugs to treat inflammatory diseases.

• Korean Journal of Plant Resources
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• v.34 no.4
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• pp.377-383
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• 2021

In this study, we investigated in vitro immunostimulatory activity of fruit extracts from Pyrus ussuriensis var. hakunensis (Nakai) T.B. Lee (PUF) using mouse macrophage RAW264.7 cells. PUF increased the production of immunostimulatory factors such as NO, iNOS, IL-1β, IL-6 and TNF-α, and phagocytic activity in RAW264.7 cells. The inhibition of TLR2 and TLR4 blocked PUF-mediated production of immunostimulatory factors in RAW264.7 cells. In addition, the inhibition of MAPKs signaling pathway reduced PUF-mediated production of immunostimulatory factors. From these results, PUF may have immunostimulatory activity via TLR2/4-mediated activation of MAPKs signaling pathway. Therefore, PUF expected to be used as a potential immune-enhancing agent.

• Natural Product Sciences
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• v.13 no.4
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• pp.283-288
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• 2007

Acanthopanacis Cortex (AC) has been popularly used as an herbal medicine for medical treatment of rheumatoid arthritis, insomnia, impotence and diabetes. Here, we investigated immunostimulating effects of the aqueous extract of AC on macrophage. We studied nitric oxide (NO) and tumor necrosis factor (TNF)-${\alpha}$ release in response to AC treatment, as they are important secretory products of macrophage. AC alone induce the NO and TNF-${\alpha}$ production. AC increase c-Jun NH2-terminal kinase 1/2 (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation but does not p38 activation in RAW 264.7 cells. Also AC resulted in the enhanced cell-surface expression of CD80 and CD14. In addition, AC resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon (IFN)-gamma. After feeding with AC to mouse for 10 days, the change of $CD28^+$ and $CD40^+$ population was analyzed. AC increased $CD28^+$ population in splenocytes in vivo. These studies indicate that AC induces macrophage activation and suggest the possible use of AC in macrophage-based immunotherapies.