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      • Identification and Characterization of a Splicing Variant in the 5′ UTR of the Human <i> TLR5</i> Gene

        Hoang, Thi Xoan,Duong, Cao Nguyen,Kim, Jae Young Hindawi 2017 BioMed research international Vol.2017 No.-

        <P>Toll-like receptors (TLRs) are essential components of the innate immune system. TLR5 is the receptor for flagellin, the principal protein component of bacterial flagella. The<I> TLR5</I> gene has 6 exons. In an RT-PCR analysis, we found long<I> TLR5 </I>transcripts, in addition to those of the expected size (short<I> TLR5</I> transcripts). A sequence analysis revealed that the long<I> TLR5</I> transcripts contain a new exon of 94 nucleotides located between previously reported exons IV and V in the 5′ untranslated region (5′ UTR). A real-time PCR analysis of the two alternatively spliced variants in various cell lines showed that the long<I> TLR5 </I>transcripts are abundantly expressed in nonimmune cells. The ratios of long/short transcripts in human nonimmune cell lines, such as A549, T98G, HaCaT, H460, HEK-293, and Caco-2 cells, and primary mesenchymal stem cells were in the range of 1.25 to 4.31. In contrast, those of human monocytic THP-1 and U937 cells and E6.1 T cells and Ramos B cells were around 0.9. These ratios in human monocytic THP-1 cells were decreased by treatment with IFN-<I>γ</I> in a concentration-dependent manner. Based on our findings, we suggest that the newly found long<I> TLR5</I> transcripts may be involved in the negative regulation of TLR5 expression and function. </P>

      • All-Trans Retinoic Acid Enhances Matrix Metalloproteinase 2 Expression and Secretion in Human Myeloid Leukemia THP-1 Cells

        Vu, Hien Thi,Hoang, Thi Xoan,Kim, Jae Young Hindawi 2018 BioMed research international Vol.2018 No.-

        <P>All-trans retinoic acid (ATRA) is an effective drug for the induction therapy of acute promyelocytic leukemia. However, the treatment is associated with adverse events such as retinoic acid syndrome (RAS) in some patients, whose histologic characteristics included organ infiltration by leukemic cells. Matrix metalloproteinase 2 (MMP-2) is often upregulated in tumor cells and plays a role in tumor cell migration and invasion by degrading the extracellular matrix. In this study, we examined the possible modulatory effects of ATRA on MMP-2 expression and secretion in human myeloid leukemia cell line THP-1. The cells were treated with various concentrations of ATRA, and MMP-2 expression and secretion were examined. MMP-2 expression and secretion started to increase with ATRA concentration as low as 0.1 nM and gradually increased thereafter. Agonists of retinoic acid receptor (RAR) or retinoid X receptor (RXR) alone could enhance MMP-2 secretion, and RAR or RXR antagonists alone could reverse ATRA-induced MMP-2 secretion. ATRA increased intracellular calcium ion levels, and a calcium-channel blocker inhibited ATRA-induced MMP-2 secretion. Dexamethasone suppressed ATRA-induced MMP-2 secretion. Our results suggest that ATRA enhances MMP-2 expression and secretion in human myeloid leukemia THP-1 cells in a calcium ion dependent manner through RAR/RXR signaling pathways, and this enhanced expression and secretion may be associated with the possible mechanisms of RAS.</P>

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        Antifungal Activity of Chitosan against Trichophyton rubrum

        ( Sanjay Monga ),( Thi Xoan Hoang ),( Jae Kweon Park ),( Jae Young Kim ) 한국키틴키토산학회 2020 한국키틴키토산학회지 Vol.25 No.4

        In the present study, we examined antifungal activity of chitosan against Trichophyton rubrum (T. rubrum), which is a dermatophytic fungus and colonizes the upper layer of dead skin and causes athlete’s foot. Water-soluble chitosan oligosaccharide (AS-WSC), which had been prepared by the hydrolysis of high molecular weight water-soluble chitosan, was used in this study. The results upon screening, the AS-WSC inhibited T. rubrum, with zones of inhibition of 2% and 0.2% AS-WSC were 22 and 6 mm, respectively, while that of fluconazole was 30 mm. Minimal inhibitory concentration (MIC) values of AS-WSC was 1.25 mg/ml, while fluconazole showed MIC value of 2 μg/ml. Inhibition percentages of radial growth by 2% and 0.2% AS-WSC were 61% and 38%, respectively, while that of fluconazole was 73%. Two% and 0.2% AS-WSC treatment resulted in reduction of mycelium dry weights by 77% and 56%, respectively, while fluconazole reducing that by 84%. Our results suggest that ASWSC can be a potential antifungal agent to treat infection by T. rubrum.

      • Hsp90 Inhibition Reduces TLR5 Surface Expression and NF- <i>κ</i> B Activation in Human Myeloid Leukemia THP-1 Cells

        Na, Bon Hyang,Hoang, Thi Xoan,Kim, Jae Young Hindawi 2018 BioMed research international Vol.2018 No.-

        <P>Tumors highly express active heat shock protein 90 (Hsp90), which is involved in tumor survival and progression. Enhanced Toll-like receptor (TLR) 5 expression and signaling were reported to be associated with acute myeloid leukemia. In the present study, we investigated the possible modulatory effects of Hsp90 inhibitors on TLR5 expression and signaling in the human myeloid leukemia cell line THP-1. Cells were pretreated with various concentrations of the Hsp90 inhibitor geldanamycin (GA) or the Hsp70 inhibitor VER155008, followed by stimulation with bacterial flagellin. Flagellin-induced nuclear factor-<I>κ</I>B (NF-<I>κ</I>B) activation was significantly reduced by treatment with GA or VER155008. To elucidate the underlying mechanism of this effect, mRNA and cell surface expression of TLR5 was examined. TLR5 mRNA expression was enhanced by both GA and VER155008, whereas cell surface expression of TLR5 was reduced by three different Hsp90 inhibitors, including GA, 17-(allylamino)-17-demethoxygeldanamycin, and radicicol, and an Hsp70 inhibitor. The inhibitory effect of Hsp90 inhibitors was much higher than that of Hsp70 inhibitor. Our results suggest that Hsp90 inhibitors suppress TLR5 surface expression and activation of NF-<I>κ</I>B in THP-1 cells in response to TLR5 ligand, and these inhibitory effects may be associated with the possible mechanisms by which Hsp90 inhibitors suppress myeloid leukemia.</P>

      • KCI등재

        Anti-inflammatory Effect of Water-soluble Chitosan Oligosaccharideson Human Monocyte THP-1 Cells

        ( Que Thanh Thanh Nguyen ),( Thi Xoan Hoang ),( Jae Kweon Park ),( Jae Young Kim ) 한국키틴키토산학회 2020 한국키틴키토산학회지 Vol.25 No.3

        The various functional properties of chitosan have been investigated for use in biomedical applications. Indeed, chitosan or its derivatives have shown anti-inflammatory effect by regulating a range of cytokines, chemokines or growth factors. In the present study, we prepared water-soluble chitosan oligosaccharide (AS-WSC) by the hydrolysis of high molecular weight water-soluble chitosan (HMW-WSC) and examined its anti-inflammatory effect on LPS-stimulated human monocytic THP-1 cells. Our results revealed that LPS-induced NF-κB activity of THP-1 cells was significantly suppressed by treatment with 0.02% AS-WSC. In addition, 0.02% AS-WSC treatment down-regulated the expression of Toll-like receptor 4 and inflammatory cytokines, such as IL-1β and TNF-α, but had no effect on IL-10 and IL-4 expression in LPS-stimulated THP-1 cells. Our results suggest that 0.02% AS-WSC can be considered as a promising anti-inflammatory agent.

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