• Journal of Applied Biological Chemistry
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• v.61 no.2
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• pp.181-186
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• 2018

In this study, we investigated the anti-inflammatory activity of berberine using human monocytes. Infection of Propionibacterium acnes induced the production of nitric oxide (NO) and the pro-inflammatory cytokines such as, $TNF-{\alpha}$, IL-8 and $IL-1{\beta}$ in THP-1 monocytic cells. However, when berberine was supplemented in these P. acnes-induced THP-1 cells, the production of pro-inflammatory cytokines and NO was significantly reduced. We also analyzed signaling pathways of the antiinflammatory function of berberine and found that berberine suppressed the phosphorylation of ERK1/2, JNK and p38 and the expression and nuclear translocation of $NF-{\kappa}B$ p65 in the P. acnes-induced cells. From these results, we concluded that berberine can effectively exert the anti-inflammatory activity via suppressing the $NF-{\kappa}B$ and mitogen-activated protein kinases signaling pathways in human monocytes. Moreover, these results suggest the feasibility of developing natural therapeutics using berberine for the treatment of P. acnes-induced inflammatory diseases.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.29-37
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• 2015

Background: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosidesd-the major active components of ginsengd-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). Methods: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on $CD14^+$ monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect $CD4^+$ T cell activity. Results: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-${\alpha}$ production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes.We confirmed that DCs derived from $CD14^+$ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-${\gamma}$) production by $CD4^+$ T cells with the coculture of Gin-DCs with $CD4^+$ T cells. Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate $CD4^+$ T cells.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.410-415
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• 2008

Previously, we identified albumin as an inhibitory factor in serum for cell adhesion of T cells such as human Jurkat T and primary cultured human T cells. In the present study, we found that other hematopoietic cell lines including U-937 human monocytes, THP-1 human monocytes, K-562 promyelocytic leukemia cells, and HL-60 human leukemia cells, also adhere to tissue culture flasks when serum is withdrawn, and albumin exerts an inhibitory effect on cell adhesion by those cells, implying that this inhibition is a common phenomenon in hematopoietic cells. Furthermore, we found that cell adhesion is inhibited by antioxidants such as (-)-epigallocatechin- 3-gallate (EGCG), morin, and a-tocopherol. Our results suggest that albumin may inhibit basal cell adhesion of hematopoietic cells and that the oxidative balance in the plasma may be important for cell adhesion of hematopoietic cells in vivo.

• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.564-570
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• 2015

Peptidoglycan (PG), the gram positive bacterial pathogen-associated molecular patterns (PAMP), is detected in a high proportion in macrophage-rich atheromatous regions, and expression of chemokine CXCL8, which triggers monocyte arrest on early atherosclerotic endothelium, is elevated in monocytes/ macrophages in human atherosclerotic lesion. The aim of this study was to investigate whether PG induced CXCL8 expression in the cell type and to determine cellular signaling pathways involved in that process. Exposure of THP-1 cell, human monocyte/macrophage cell line, to PG not only enhanced CXCL8 release but also profoundly induced il8 gene transcription. PG-induced release of CXCL8 and induction of il8 gene transcription were blocked by OxPAPC, an inhibitor of TLR-2/4 and TLR4, but not by polymyxin B, an inhibitor of LPS. PG-mediated CXCL8 release was significantly attenuated by inhibitors of PI3K-Akt-mTOR pathways. PKC inhibitors, MAPK inhibitors, and ROS quenchers also significantly attenuated expression of CXCL8. The present study proposes that PG contributes to inflammatory reaction and progression of atherosclerosis by inducing CXCL8 expression in monocytes/macrophages, and that TLR-2, PI3K-Akt-mTOR, PKC, ROS, and MAPK are actively involved in the process.

• Proceedings of the Zoological Society Korea Conference
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• 2000.10a
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• pp.281.1-281
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• 2000

No Abstract, See Full Text

• Journal of Nutrition and Health
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• v.24 no.2
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• pp.97-103
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• 1991

The increase in alcohol consumption level has been noticed in Korea recently. Alcohol appreciably inhibits cell mediated immunity and this may contribute to the high prevalence of serious infection such as pulmonary tuberculosis among alcoholic subjects. The present study was undertaken to examine the effect of ethanol on the cyclooxygenase metabolites of human monocyte in vitro. Monocytes were activated with 800 units of gamma interferon(IFN-${\gamma}$) for 3 days following apply of Ficool-hypaque density gradient and gelatin coated flasks for separation of monocytes. Ethanol with addition of 100mM, 300mM and 600 mM for 30 minutes to 106 monocytes with/without previous IFN-${\gamma}$ treatment caused a dose dependent decrease in the production of thromboxane B2, 6-keto-PGE1$\alpha$ and PGE2 by radioimmunoassay at 6 hours after ethanol treatment. Quite different from the findings after 6 hours there was dose dependent increase in three prostaglandins without IFN-${\gamma}$ treatment after 24 hours of incubation. With previous treatment of IFN-${\gamma}$ reduced productions of three prostaglandins at 24 hours than control is spite of ethanol stimjulation. These findings show that IFN-${\gamma}$ can inhibit alcohol induced derangement of arachidonic acid metabolism of monocytes.

• Biomedical Science Letters
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• v.15 no.1
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• pp.93-96
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• 2009

House dust mites (HDMs) play an important role in the occurrence of allergic diseases such as asthma and atopic dermatitis. Dermatophagoides pteronyssinus (Der p) is one of the most prevalent HDMs. It mediates the activation of T cells and monocytes, and induces the elevation of immunoglobulin E levels in allergic diseases. However, the effects of Der p on human monocytes have not been fully understood. In the present study, we investigated whether or not Der p has a great effect on the chemotactic activity of the human monocytic cell line, THP-1 cells, as induced by CC chemokines. We also show that the Der p extract (DpE) increased the chemotactic activity of THP-1 cells in response to MCP-1, RANTES, MIP-1${\alpha}$, and TARC, but had no effect on the expressions of CC chemokine receptors (CCRs) binding to CC chemokines in THP-1 cells. Protease inhibitors, such as aprotinin and E64, blocked the increased chemotaxis, while cytoplasmic $Ca^{2+}$ influx mediated by these chemokines was inhibited by DpE. These results indicate that DpE increases the chemotactic activity of THP-1 cells in response to CC chemokines by regulating the cells' protease-dependent mechanism. This finding may be useful in identifying the pathogenesis of allergic diseases induced by Der p.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.237-246
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• 2005

Background: Little information is available on the identification and characterization of the upstream regulators of the signal transduction cascades for Mycobacterium tuberculosis (M. tbc)-induced ERK 1/2 activation and chemokine expression. We investigated the signaling mechanisms involved in expression of CCL3 /MIP-1 and CCL4/MIP-1 in human primary monocytes infected with M. tbc. Methods: MAP kinase phosphorylation was determined using western blot analysis with specific primary antibodies (ERK 1/2, and phospho-ERK1/2), and the upstream signaling pathways were further investigated using specific inhibitors. Results: An avirulent strain, M. tbc H37Ra, induced greater and more sustained ERK 1/2 phosphorylation, and higher CCL3 and CCL4 production, than did M. tbc H37Rv. Specific inhibitors for mitogen-activated protein kinase (MAPK) kinase (MEK; U0126 and PD98059) significantly inhibited the expression of CCL3 and CCL4 in human monocytes. Mycobactetia-mediated expression of CCL3 and CCL4 was not inhibited by the Ras inhibitor manumycin A or the Raf-1 inhibitor GW 5074. On the other hand, phospholipase C (PLC) inhibitor (U73122) and protein kinase C (PKC)specific inhibitors ($G\ddot{o}6976$ and Ro31-8220) significantly reduced M. tbc-induced activation of ERK 1/2 and chemokine synthesis. Conclusion: These results are the first to demonstrate that the PLC-PKC-MEK-ERK, not the Ras-Raf-MEK-ERK, pathway is the major signaling pathway inducing M. tbc-mediated CCL3 and CCL4 expression in human primary monocytes.

• 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.

• IMMUNE NETWORK
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• v.13 no.2
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• pp.75-79
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• 2013

Evidence for immunoregulatory roles of prostaglandins (PGs) is accumulating. Since our observation of PG production by human follicular dendritic cells (FDCs), we investigated the regulatory mechanism of PG production in FDC and attempted to understand the functions of released PGs in the responses of adjacent lymphocytes. Here, using FDC-like cells, HK cells, we analyzed protein expression alterations in cyclooxygenase-2 (COX-2) in the presence of IL-4 or histone deacetylase (HDAC) inhibitors. Both IL-4 and HDAC inhibitors suppressed COX-2 expression in dose-dependent manners. Their effect was specific to COX-2 and did not reach to COX-1 expression. Interestingly, HDAC inhibitors gave rise to an opposing effect on COX-2 expression in peripheral blood monocytes. Our results suggest that IL-4 may regulate COX-2 expression in FDCs by affecting chromatin remodeling and provide insight into the role of cellular interactions between T cells and FDC during the GC reaction. Given the growing interests in wide-spectrum HDAC inhibitors, the differential results on COX-2 expression in HK cells and monocytes raise cautions on their clinical use.