• Clinical and Experimental Pediatrics
• /
• v.52 no.6
• /
• pp.667-673
• /
• 2009

Purpose : Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacterial infections. The purpose of this study was to analyze TLR2 surface expressions and TLR2-mediated tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6) production in patients with BCG vaccine-associated suppurative lymphadenitis. Methods : Peripheral monocytes were separated from 16 patients with BCG vaccine-associated suppurative lymphadenitis and 10 healthy controls using a magnet cell isolation kit. Monocytes ($1{\times}10^6$ cells/well) were incubated with a constant amount of $Pam_3CSK_4$ ($100{\mu}g/mL$) for 24 hours. TLR2 surface expression on monocytes was analyzed by FACS analysis and TLR-2 mRNA expression was determined by RT-PCR. TLR2-mediated $TNF-{\alpha}$ and IL-6 production were measured by ELISA. Results : In patients with BCG vaccine-associated suppurative lymphadenitis, low TLR2 expression on monocytes ($3.39{\pm}$1.2% versus $4.64{\pm}2.6%$) together with significantly lower TLR2 mRNA expression than in the healthy controls was seen after $Pam_3CSK_4$ stimulation. TLR2-mediated $TNF-{\alpha}$ and IL-6 production in patients with BCG vaccine-associated suppurative lymphadenitis ($TNF-{\alpha}$, $775.5{\pm}60.8pg/mL$; IL-6, $4,645.8{\pm}583.9pg/mL$) were also lesser than that in healthy controls ($TNF-{\alpha}$, $1,098.5{\pm}94.3pg/mL$; IL-6, $6,696.3{\pm}544.3pg/mL$). Conclusion : These findings suggest that low TLR2 expression on monocytes might be associated with increased susceptibility to BCG vaccine-associated suppurative lymphadenitis.

• Clinical and Experimental Pediatrics
• /
• v.48 no.7
• /
• pp.779-788
• /
• 2005

Purpose : Echinacea, a traditional plant medicine has been used as immune-stimulant. Recent studies have revealed that extract of Echinacea has immunostimulatory effects on human blood mononuclear cells. This study was designed for the purpose of screening the genes associated with immunologic effects of Echinacea on monocytes and dendritic cells using a cDNA microarray chip. Methods : $CD14^+$ monocyte cells were cultured for one day with Echinacea extract(final concentration : $50{\mu}g/mL$) in experiment 1, but were cultured without Echinacea in experiment 2. The gene expression of these cultured monocytes was analyzed using the cDNA microarray chip. Dendritic cells produced from $CD14^+$ monocyte were cultured for five days with GM-CSF and IL-4, and then cultured for one day with Echinacea in experiment 3, but were done without Echinacea in experiment 4. Results : In experiments 1 and 2, there were 17 significantly expressed genes with average expression ratios above 2.5, including interferon gamma-inducible protein 30(IFI 30), CDC(cell-division-cylcle)-like kinase 2(CLK 2), syndecan binding protein(syntenin), superoxide dismutase 2, etc. In experiments 3 and 4, there were 24 gene, with significantly expressed genes were 24 genes, which were insulin-like growth factor 2(somatomedin A), methyl-CpG binding domain protein 3, IFI 30, small inducible cytokine subfamily A, member 22, etc. The genes encoding CD44, IFI 30, mannose receptor C type 1(MRC 1), chemokine receptor 7(CCR 7), CLK 2, syntenin and cytochrome C oxidase subunit VIII were significantly expressed in both monocytes and dendritic cells cultured with Echinacea. Conclusion : This study employed a cDNA microarray chip to elicit the immune-associated gene profile; the expression was enhanced by Echinacea in CD14+ monocytes and dendritic cells. Thus we laid the basis for the quantitative and functional analysis of genes induced by Echinacea in monocytes and monocyte-derived dendritic cells.

• Korean Journal of Clinical Laboratory Science
• /
• v.49 no.2
• /
• pp.128-134
• /
• 2017

Der p 1 and Der p 2 are essential allergens of house dust mite associated with the development of asthma. In the present study, we examined whether Der p 1 and Der p 2 induce a release of S100A8 and S100A9 in monocytes, which are involved in the regulatory mechanism of neutrophil apoptosis. We found that Der p 1 and Der p 2 significantly increased the secretion of S100A8 and S100A9 in normal monocytes. Moreover, S100A8 and S100A9 strongly suppressed the spontaneous apoptosis of normal and asthmatic neutrophils. The inhibitory effect of S100A9 was stronger than that of S100A8, and asthmatic neutrophils showed a higher inhibitory effect than normal neutrophils. S100A8 and S100A9 induced activation of Lyn, Akt, and ERK in a time-dependent manner. These findings elucidate the roles of Der p 1 and Der p 2 in the interaction between monocytes and neutrophils, as well as contributing to our knowledge of the pathogenesis of allergic diseases.

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

• Safety and Health at Work
• /
• v.8 no.2
• /
• pp.198-205
• /
• 2017

Background: There are a million ragpickers in India who gather and trade recyclable municipal solid wastes materials for a living. The objective of this study was to examine whether their occupation adversely affects their immunity. Methods: Seventy-four women ragpickers (median age, 30 years) and 65 age-matched control housemaids were enrolled. Flow cytometry was used to measure leukocyte subsets, and leukocyte expressions of $Fc{\gamma}$ receptor I (CD64), $Fc{\gamma}RIII$ (CD16), complement receptor 1 (CD35) and CR3 (CD11b/CD18), and CD14. Serum total immunoglobulin-E was estimated with enzyme-linked immunosorbent assay. Results: Compared with the controls, ragpickers had significantly (p < 0.0001) higher levels of CD8-T-cytotoxic, CD16+CD56+natural killer, and CD4+CD45RO+memory T-cells, but depleted levels of CD19+B-cells. The percentage of CD4+T-helper-cells was lower than the control group (p < 0.0001), but their absolute number was relatively unchanged (p = 0.42) due to 11% higher lymphocyte counts in ragpickers. In ragpickers, the percentages of CD14+CD16+intermediate and CD14dim CD16+nonclassical monocyte subsets were elevated with a decline in CD14+CD16-classical monocytes. The expressions of CD64, CD16, CD35, and CD11b/CD18 on both monocytes and neutrophils, and CD14 on monocytes were significantly higher in ragpickers. In addition, ragpickers had 2.7-times more serum immunoglobulin-E than the controls (p < 0.0001). After controlling potential confounders, the profession of ragpicking was positively associated with the changes. Conclusion: Ragpicking is associated with alterations in both innate (neutrophils, monocytes, and natural killer cell numbers and expression of complement and $Fc{\gamma}$ receptors) and adaptive immunity (numbers of circulating B cells, helper, cytotoxic, and memory T cells).

• Korean Journal of Food Science and Technology
• /
• v.46 no.6
• /
• pp.773-777
• /
• 2014

The anti-inflammatory activity of onion juices prepared from sulfur-fertilized onions was investigated by measuring the secretion of proinflammatory cytokines from human monocytes cultured under hyperglycemic condition. Human monocytic (THP-1) cells were cultured under normoglycemic (NG, 5.5 mM glucose) or hyperglycemic (HG, 25 mM glucose) conditions, with or without onion juice. Without onion juice, cell viability decreased significantly in the HG state for 48 h, compared to that in the NG state. With onion juice ($50-150{\mu}L$) treatment, the cell viability was not different from that under the NG condition, suggesting that onion juice prevented HG-induced monocytes cytotoxicity. While the HG condition in vitro significantly induced TNF-${\alpha}$ release from THP-1 cells and its gene expression, onion juice ($50{\mu}L$) significantly suppressed them. This indicates that onion juice inhibited HG-induced cytokine production in monocytes. These results suggest that onion juice from sulfur-fertilized onions can be used for the prevention of diabetes and related diseases.

• Journal of Life Science
• /
• v.32 no.6
• /
• pp.421-429
• /
• 2022

The expression of interleukin-1α (IL-1α) is elevated in monocytic cells, such as monocytes and macro-phages, within atherosclerotic arteries, yet the cellular molecules involved in cytokine upregulation remain unclear. Because peptidoglycan (PG), a major component of gram-positive bacterial cell walls, is detected within the inflammatory cell-rich regions of atheromatous plaques, it was investigated if PG contributes to IL-1α expression in monocytes/macrophages. Exposure of THP-1 monocytic cells to PG resulted in elevated levels of IL-1α gene transcripts and increased secretion of IL-1α protein. The transcription and secretion of IL-1α were abrogated by OxPAPC, an inhibitor of TLR2/4, but not by polymyxin B that inhibits lipopolysaccharide-induced TLR4 activation. To understand the molecular mechanisms of the inflammatory responses due to bacterial pathogen-associated molecular patterns (PAMPs) in diseased arteries, we attempted to determine the cellular factors involved in the PG-induced upregulation of IL-1α expression. Pharmacological inhibition of cell signaling pathways with LY294002 (a PI3K inhibitor), Akti IV (an inhibitor of Akt activation), rapamycin (an mTOR inhibitor), U0126 (a MEK inhibitor), SB202190 (a p38 MAPK inhibitor), SP6001250 (a JNK inhibitor), and DPI (a NOX inhibitor) also significantly attenuated the PG-mediated expression of IL-1α. These results suggest that PG induces the monocytic or macrophagic expression of IL-1α, thereby contributing to vascular inflammation, via multiple signaling molecules, including TLR2, PI3K/Akt/mTOR, and MAPKs.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.125.2-126
• /
• 2003

Human tumor necrosis factor-alpha (TNFa) is a key pro-inflammatory cytokine produced by activated monocytes and macrophage as a part of the self-defence machinery. TNF-a converting enzyme (TACE) is the metalloproteinase that processes the membrane bound precursor of TNFa to the soluble component. (omitted)

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

No Abstract, See Full Text

• Journal of Nutrition and Health
• /
• v.31 no.8
• /
• pp.1235-1243
• /
• 1998

Although an elevated plasma level of high density lipoprotein (HDL) is known as a protective component against the development of atherosclerosis and ensuing coronary heart diseases, the related mechanisms are still not established . It has been clearly demonstrated in the early stages of atherogenesis that adhesion of monocytes and lymphocytes to the vascular endothelium is enhanced via adhesion molecules, and that monocytes and macrophages accumulate in the subendothelial space. The present study has investigated whether isolated plasma HDL plays a role in protection against atherogenesis by inhibiting the expression of vascular cell adhesioin molecule-1(VCAM-1) on the endothelial cells. Effects of plasma native low density lipoprotein (LDL) and ac ethylated LDL(AcLDL) on VCAM-1 expression were also examined by using an immunocytochemical technique. While plasma HDL did not alter the basal expression of VCAM-1 , lipopolysaccharide(LPS) induction of this adhesion modlecule was markedly inhibited at a phyaiological concentration of HDL. In contrast, 30$\mu\textrm{g}$ protein/ml AcLDL increased sifnificantly both basal VCAM-1 expression and its LPD induction , suggesting that this modified LDL enhances leukocyte adhesiion to endothelial cells. Unlike AcLDL , plasma native LDL inhibited significantly VCAM-1 expression. This indicates that LDL did not undergo oxidative modificantion while incubated with endothelial cells. These results suggest that plasam HDL may inhibit atherogenesis by reducing the expression of adhesion molecules, which is a protective mechanism independent of tis reverse cholesterol transport function . Modified LDL is a potent iducer for adhesion molecules in vascular endothelical cells and could play a role in the pathogenesis of atherosclerosis by adhering to blood cells.