• Journal of Microbiology
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• v.40 no.3
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• pp.224-229
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• 2002

The effect of human cytomegalovirus (HCMV) on three human monocyte cell lines at different stages of differentiation was investigated. While the viability of HL-60 cells or U-937 cells was not significantly affected by HCMV infection, the viability of THP-1 cells was reduced. Acridine orange/ethidiurn bromide staining revealed that the reduction of THP-1 cell viability was due to increased apoptotic death following HCMV infection. Apoptosis in HL-60 cells was not affected by HCMV infection, and induction of apoptosis of U-937 cells by HCMV was intermediate between HL-60 and THP-1 cells. Since HL-60 cells are the least differentiated and THP-1 cells are the most differentiated, the induction of apoptosis of human monocytes appears to be related to the degree of cell differentiation. Flow cytometric and confocal microscopic studies using fluorescent calcium indicator Fluo-3 suggested a significant increase in intracellular free calcium concentration (［Ca$\^$2+/］i) in THP-1 cells undergoing apoptosis by HCMV infection. Again ［Ca$\^$2+/］i in HCMV-infected HL-60 cells was not critically altered, and that in HCMV-infected U-937 cells was intermediate between THP-1 cells and HL-60 cells. Calcium influx blockers such as verapamil and nifedipine partially reversed HCMV-induced apoptosis in THP-1 cells.

• BMB Reports
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• v.42 no.9
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• pp.574-579
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• 2009

The regulatory effects of honokiol on the cellular responses of macrophages and monocytes were evaluated. Specifically, we investigated the effects of honokiol with respect to lipopolysaccharide (LPS)-induced cytotoxicity, LPS- or phorbol-12-myristate-13-acetate (PMA)-mediated morphological changes, and relevant events (FITC-dextran-induced phagocytic uptake). Honokiol blocked the LPS-induced cytotoxicity of RAW264.7 cells in a dose-dependent manner. In addition, honokiol appeared to block the production of cytotoxic cytokines such as interleukin (IL)-$1{\beta}$ and tumor necrosis factor (TNF)-$\alpha$, nitric oxide (NO), and reactive oxygen species (ROS). Moreover, honokiol strongly prevented the morphological changes in RAW 264.7 and U937 cells that were induced by LPS and PMA. The surface levels of marker proteins, which are up-regulated under the morphological changes of RAW264.7 and U937 cells, were also diminished. The data presented here strongly suggest that the honokiol modulates various cellular responses managed by macrophages and monocytes.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.657-665
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• 2006

We recently reported that dimethylsphingosine (DMS), a metabolite of sphingolipids, increased intracellular pH and $Ca^{2+}$ concentration in U937 human monocytes. In the present study, we found that dimethylphytosphingosine (DMPH) induced the above responses more robustly than DMS. However, phytosphingosine, monomethylphytosphingosine or trimethylsphingosine showed little or no activity. Synthetic C3 deoxy analogues of sphingosine did show similar activities, with the C16 analogue more so than C18. The following structure-activity relationships were observed between DMS derivatives and the intracellular pH and $Ca^{2+}$ concentrations in U937 monocytes; 1) dimethyl modification is important for the DMS-induced increase of intracellular pH and $Ca^{2+}$, 2) the addition of an OH group on C4 enhances both activities, 3) the deletion of the OH group on C3 has a negligible effect on the activities, and 4) C16 appears to be more effective than C18. We also found that W-7, a calmodulin inhibitor, blocked the DMS-induced pH increase, whereas, KN-62, ML9, and MMPX, specific inhibitors for calmodulin-dependent kinase II, myosin light chain kinase, and $Ca^{2+}$-calmodulin-dependent phosphodiesterase, respectively, did not affect DMS-induced increases of pH in the U937 monocytes.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.2
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• pp.41-56
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• 2010

Objectives : On an experimental basis, the effects of atopic dermatitis induced materials on the expression of cytokine genes in human monocytes (THP-1, U937) and mast cells were studied. This study was carried out to be considered a fundamental knowledge in the research on the good of oriental medicine. Methods : After culturing THP-1, U937, and HMC-1, with the three different concentrations of LPS ($1\;{\mu}g/ml$), DPE ($10\;{\mu}g/ml$), and DNCB ($1\;{\mu}g/ml$), atopic dermatitis induced materials were treated in the culture medium. To investigate cytokine genes expression patterns, with lysis buffer and separation reagent, total RNA was extracted from THP-1, U937, and HMC-1 at intervals of 0, 12, 24, and 48 hours. Both cytokine mRNA expression patterns by atopic dermatitis induced materials and change of cytokine genes expression patterns in relation to atopy by selenium were analyzed with RT-PCR. Also IL-4 and INF-$\gamma$, which were secreted in the HMC-1, were analyzed using ELISA method. Results : 1. After treating THP-1 and U937 with LPS, DPE, and DNCB, there was no significant change in cytokine genes themselves, but various cytokines (IL-4, IL-6, IL-8, IL-13, IFN-$\gamma$, IFN-a, MCP-1, B2-MG) were expressed. 2. In the case of HMC-1, the expressions of IL-6 and IL-8 were significantly increased in the analysis of mRNA expression by dust mite allergens in DPE. 3. As a result of ELISA method, it is certain that IL-4 and IFN-$\gamma$ protein were secreted in the HMC-1 by DPE. 4. Selenium, an essential trace element, decreased the IL-10 and IL-13 expression in the HMC-1 by DPE. Conclusion : The results suggest that it is necessary to choose proper atopic dermatitis induced materials and suitable cultured cells in establishment of in vitro model of atopic dermatitis.

• YAKHAK HOEJI
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• v.52 no.5
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• pp.412-417
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• 2008

BAY11-7082 was initially found to be an anti-inflammatory drug with NF-${\kappa}B$ inhibitory property. In this study, we evaluated modulatory function of BAY11-7082 on U937 cell-cell adhesion induced by CD29 (${\beta}1$-integrins). BAY11-7082 strongly blocked functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay. However, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. In particular, to understand molecular mechanism of BAY11-7082-mediated inhibition, the regulatory roles of CD29-induced actin cytoskeleton rearrangement under cell-cell adhesion and surface level of CD29 were examined using confocal and flow cytometic analysis. Interestingly, this compound strongly suppressed the molecular association of actin cytoskeleton with CD29 at cell-cell adhesion site. Moreover, BAY11-7082 also diminished surface levels of CD29 as well as its-associated adhesion molecule CD147, but not other adhesion molecules such as CD18 and CD43. Therefore, our data suggest that BAY11-7082 may be involved in regulating immune responses managed by CD29-mediated cell-cell adhesion.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.515-523
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• 2016

Adhesion events of monocytes represent an important step in inflammatory responses induced by chemokines. The ${\beta}1$-integrin CD29 is a major adhesion molecule regulating leukocyte migration and extravasation. Although several adhesion molecules have been known as regulators of CD29, the molecular interactions between CD29 and its regulatory adhesion molecules (such as CD98 and CD147) have not been fully elucidated. Therefore, in this study, we examined whether these molecules are functionally, biochemically, and cell-biologically associated using monocytic U937 cells treated with aggregation-stimulating and blocking antibodies, as well as enzyme inhibitors. The surface levels of CD29, CD98, and CD147 (but not CD43, CD44, and CD82) were increased. The activation of CD29, CD98, and CD147 by ligation of them with aggregation-activating antibodies triggered the induction of cell-cell adhesion, and sensitivity to various enzyme inhibitors and aggregation-blocking antibodies was similar for CD29-, CD98-, and CD147-induced U937 cell aggregation. Molecular association between these molecules and the actin cytoskeleton was confirmed by confocal microscopy and immunoprecipitation. These results strongly suggest that CD29 might be modulated by its biochemical and cellular regulators, including CD98 and CD147, via the actin cytoskeleton.

• Journal of the Korean Society of Radiology
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• v.13 no.1
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• pp.133-140
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• 2019

Triglycerides (TG) are one of the triggers of chronic inflammatory lesions in the blood vessels. In the key factors in the development of inflammatory diseases, Pro-inflammatory cytokines such as tumor necrosis factor-alpha $(TNF-){\alpha}$ and interleukin-1 beta ($IL-1{\beta}$) contribute to the development of inflammatory lesions by recruiting other immune cells in the inflamed area or causing cell necrotic death. In this study, I investigated the effect of Jurkat T lymphocytes and U937 monocytes involved in vascular inflammation development on the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ on exposure to TGs. In Jurkat cells, mRNA expression of $TNF-{\alpha}$ is increased by exposure to TGs. However, the expression levels of $TNF-{\alpha}$ and $IL-1{\beta}$ were increased by TGs in U937 cells. To investigate whether inducible nitric oxide synthase (iNOS) is involved in the increase of expression of $TNF-{\alpha}$ and $IL-1{\beta}$ by TGs, treatment of W1400 (an iNOS inhibitor) resulted in recovery of expression level both $TNF-{\alpha}$ and $IL-1{\beta}$. Based on the present study, it was confirmed that the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ in monocytes and T lymphocytes. This increased cytokines contribute to development of vascular inflammatory lesions. In addition, iNOS is involved in the increase of $TNF-{\alpha}$ and $IL-1{\beta}$ expression by TGs.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.277-283
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• 2013

In this study, we investigated the effects of a selective urotensin II (UII) receptor antagonist, SB-657510, on the inflmmatory response induced by UII in human umbilical vein endothelial cells (EA.hy926) and human monocytes (U937). UII induced inflammatory activation of endothelial cells through expression of proinflammatory cytokines (IL-$1{\beta}$ and IL-6), adhesion molecules (VCAM-1), and tissue factor (TF), which facilitates the adhesion of monocytes to EA.hy926 cells. Treatment with SB-657510 significantly inhibited UII-induced expression of IL-$1{\beta}$, IL-6, and VCAM-1 in EA.hy926 cells. Further, SB-657510 dramatically blocked the UII-induced increase in adhesion between U937 and EA.hy926 cells. In addition, SB-657510 remarkably reduced UII-induced expression of TF in EA.hy926 cells. Taken together, our results demonstrate that the UII antagonist SB-657510 decreases the progression of inflammation induced by UII in endothelial cells.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.300-307
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• 2013

20S-dihydroprotopanaxatriol (2H-PPT) is a derivative of protopanaxatrol from ginseng. Unlike other components from Panax ginseng, the pharmacological activity of this compound has not been fully elucidated. In this study, we investigated the modulatory activity of 2H-PPT on the cellular responses of monocytes and macrophages to understand its immunoregulatory actions. 2H-PPT strongly upregulated the release of radicals in sodium nitroprusside-treated RAW264.7 cells and the surface levels of costimulatory molecule CD86. More importantly, this compound remarkably suppressed nitric oxide production, morphological changes, phagocytic uptake, cell-cell aggregation, and cell-matrix adhesion in RAW264.7 and U937 cells in the presence or absence of lipopolysaccharide, anti-CD43 antibody, fibronectin, and phorbal 12-myristate 13-acetate. Therefore, our results suggest that 2H-PPT can be applied as a novel functional immunoregulator of macrophages and monocytes.

• Anatomy & Biological Anthropology
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• v.31 no.4
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• pp.143-149
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• 2018

Leucocyte extravasation has been known to play an important role in inflammatory reactions including contact dermatitis. Previous studies suggested that CD99 regulates ${\beta}1$ integrin activity and may be a novel therapeutic target molecule for inflammatory diseases. In this study, the effects of CD99-derived peptide, CD99CRIII3, on inflammatory reactions in contact dermatitis mouse model were investigated. CD99CRIII3 decreased ${\beta}1$-integrin activity in human monocytic U937 cells. CD99CRIII3 inhibited the adhesion of U937 monocytes to human umbilical vein endothelial cells and their extravasation through human umbilical vein endothelial cells. CD99CRIII3 reduced inflammation in the phorbol myristate acetate-induced contact dermatitis mice in a dose-dependent manner. These results indicate that CD99CRIII3 suppresses the extravasation of monocytes and inflammatory reactions in the animal model of the contact dermatitis, suggesting that CD99CRIII3 could be a new drug candidate against inflammatory skin diseases.