• Title, Summary, Keyword: B7H1

Search Result 3,889, Processing Time 0.079 seconds

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

  • Xiong, Hai-Yu;Ma, Ting-Ting;Wu, Bi-Tao;Lin, Yan;Tu, Zhi-Guang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.14
    • /
    • pp.5767-5772
    • /
    • 2014
  • Background and Aim: B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms. Methods: PMA induced THP-1-derived macrophages or human monocyte-derived macrophages were treated with recombinant IL-12 (rIL-12) or infected with adenovirus carrying human IL-12 gene (Ad-IL-12-GFP) for 24 h, then cocultured with the SKOV3 ovarian cancer cell line for another 24 h. Macrophages were collected for real-time PCR and Western blot to detect the expression of B7-H1, and activation of the NF-${\kappa}B$ signaling pathway. Moreover, supernatants were collected to assay for IL-12, IFN-${\gamma}$ and IL-10 by ELISA. In addition, monocyte-derived macrophages treated with IFN-${\gamma}$ were cocultured with SKOV3 and determined for the expression of B7-H1. Furthermore, the expression of B7-H1 in monocyte-derived macrophages was also evaluated after blocking NF-${\kappa}B$ signaling. Results: The expression of B7-H1 was significantly upregulated in monocyte-derived macrophages treated with rIL-12 or Ad-IL-12-GFP compared with the control groups (p<0.05), accompanied by a remarkable upregulation of IFN-${\gamma}$ (p<0.05), a marked downregulation of IL-10 (p<0.05) and activation of NF-${\kappa}B$ signaling. However, the upregulation of B7-H1 was inhibited by blocking the NF-${\kappa}B$ signaling pathway (p<0.05). Expression of B7-H1 was also increased (p<0.05) in monocyte-derived macrophages treated with IFN-${\gamma}$ and cocultured with SKOV3. By contrast, the expression of B7-H1 in THP-1-derived macrophages was significantly decreased when treated in the same way as monocyte-derived macrophages (p<0.05), and IL-10 was also significantly decreased but IFN-${\gamma}$ was almost absent. Conclusions: IL-12 upregulates the expression of B7-H1 in monocyte-derived macrophages, which is possible though inducing the secretion of IFN-${\gamma}$ and further activating the NF-${\kappa}B$ signal pathway. However, IL-12 downregulates the expression of B7-H1 in THP-1-derived macrophages, associated with a lack of IFN-${\gamma}$ and inhibition of expression of IL-10.

Effect of TLR4 and B7-H1 on Immune Escape of Urothelial Bladder Cancer and its Clinical Significance

  • Wang, Yong-Hua;Cao, Yan-Wei;Yang, Xue-Cheng;Niu, Hai-Tao;Sun, Li-Jiang;Wang, Xin-Sheng;Liu, Jing
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.3
    • /
    • pp.1321-1326
    • /
    • 2014
  • Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

New Transition Metal Mediated Alkylation Reaction of arachno-$S_{2}B_{7}H_{8}$, Insertion Reaction of arachno-$S_{2}B_{7}H_{8}^{-}$ with $(CO)_{5}M$ {${C(R_{1})(R_{2})}$} $(M=Cr,\;W;\;R_{1}=CH_{3},\;C_{6}H_{5};\;R_{2}=OCH_{3},\;SC_{6}H{5})$: Synthesis and Characterization of arachno-$4-RCH_{2}-6,8-S_{2}B_{7}H_{8}\;(R=CH_{3},\;IIa;\;C_{6}H_{5},\;IIb)$

  • Hee-Joo Jeon;Jae-Jung Ko;Kang-bong Lee;Sang Ook Kang
    • Bulletin of the Korean Chemical Society
    • /
    • v.14 no.1
    • /
    • pp.113-117
    • /
    • 1993
  • Good yield synthetic routes for the production of new B-alkyl-dithiaborane clusters are reported. The syntheses of the B-alkyl-dithiaboranes are based on the use of Fischer-type carbene reagents to activate the B-H bonds of dithiaborane for alkyl-addition reactions and are the first examples of transition-mediated reactions of dithiaborane to be reported. Thus, reactions employing arachno-$S_2B_7H_8$- and $(CO)_5M{C(R_1)R_2}$ (M = Cr, W; $R_1 = CH_3,\;C_6H_5;\; R_2 = OCH_3,\;SC_6H_5)$ were found to yield the intermidiate anions I, $[(CO)_5M{C(R_1)R_2S_2B_7H_8}]^-$, which upon protonation gave the corresponding neutral, air-sensitive cluster arachno-4-$RCH_2-6,8-S_2B_7H_8(R=CH_3,\;IIa;\;C_6H_5,\;IIb)$ range from 30 to 35% yield. Complexes IIa and IIb are isoelectronic with arachno-6,8-$S_2B_7H_9$ and, on the basis of the spectroscopic data, are proposed to adopt a similar arachno cage geometry in which an $RCH_2$ units are substituted to 4 position boron atom of the arachno-6,8-$S_2B_7H_9$.

  • PDF

Efficient Synthesis of hypho-2,5-$S_2B_7H_{11}$ and Preparation of New nido-, arachno-, and hypho-Metalladithiaborane Clusters Derived from Its Anion hypho-$S_2B_7H_{10}{^-}$

  • 강창환;김성준;고재정;강상욱
    • Bulletin of the Korean Chemical Society
    • /
    • v.16 no.11
    • /
    • pp.1067-1074
    • /
    • 1995
  • Reaction of arachno-S2B7H8- with either THF or 1,2-dimethoxyethane upon refluxing condition results in the formation of the previously known compound hypho-S2B7H10-. Protonation of hypho-S2B7H10- with HCl/Et2O generates hypho-2,5-S2B7H11 in good yield. This hypho-S2B7H10- anion has been employed to generate a series of new nido-, arachno-, and hypho-metalladithiaborane clusters. Reaction of the anion with Cp(CO)2FeCl results in direct metal insertion and the formation of a complex containing the general formula (η5-C5H5)FeS2B7H8. Spectroscopic studies of nido-6-CpFe-7,9-S2B7H8 Ⅰ demonstrated that compound Ⅰ was shown to have an nido-type cage geometry derived from an octadecahedron missing one vertex, with the iron atom occupying the three-coordinate 6-position in the cage and the two sulfurs occupying positions on the open face of the cage. Reaction of hypho-S2B7H10- with CoCl2/Li+[C5H5]- gave the previously known complex arachno-7-CpCo-6,8-S2B6H8 Ⅱ. Also, the reaction of the anion with [Cp*RhCl2]2 gave the complex arachno-7-Cp*Rh-6,8-S2B6H8 Ⅲ, the structure of which was shown to be that of complex Ⅱ. The similarity of the NMR spectra of Ⅱ and Ⅲ suggest that Ⅲ adopts cage structure similar to that previously confirmed for Ⅱ. A series of 9-vertex hypho clusters in which the sulfur atoms are bridged by different species isoelectronic with a BH3 unit, such as HMn(CO)4 or SiR2 have been prepared. Compounds Ⅳ,Ⅴ and Ⅵ are each 2n+4 skeletal electron systems and would be expected according to skeletal electron counting theory to adopt hypho-type polyhedral structures derived from an icosahedron missing three vertices. The complex hypho-1-(CO)4Mn-2,5-S2B6H9 Ⅳ was obtained by the reaction of the anion with (CO)5MnBr and has been shown from spectroscopic data to consist of a (CO)4Mn fragment bound to the two sulfur atoms S2 and S5 of hypho-S2B7H10-. Also, similar hypho-type complexes hypho-1-R2Si-2,5-S2B6H8 (R=CH3 Ⅴ, R=C6H5 Ⅵ) have been prepared from the reaction of hypho-S2B7H10- with R2SiHCl.

  • PDF

Synthesis and Tautomerism of Pyrido[2,3-b]pyrazines (Pyriodo[2,3-b]pyrazine류의 합성과 토토머화 현상)

  • Kim, Ho-Sik;Choi, Kyung-Ok;Kurasawa, Yoshihisa
    • Journal of the Korean Chemical Society
    • /
    • v.44 no.5
    • /
    • pp.435-440
    • /
    • 2000
  • The reaction of 2-methoxycarlmethylen-l,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(5) with hydrazine hydrate and ethylenediamine gave 2-hydrazinocarbonylmethylene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(6) and 2-aminoethylcarbamethylene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one(7), res-pectively. The reaction of compound 6 or 7 with substituted benzaldehydes or heteroaryl aldehydes afforded pyrido[2,3-b]pyrazines(8-13). Some pyrin the enamine, methylene imine and enaminol forms in solution. The tau-tomer ratios were determined by the H NMR.

  • PDF

Two New closo- or nido-Carborane Diphosphine Complexes: Synthesis, Characterization and Crystal Structures

  • Kong, Lingqian;Zhang, Daopeng;Su, Fangfang;Li, Dacheng;Dou, Jianmin
    • Bulletin of the Korean Chemical Society
    • /
    • v.32 no.7
    • /
    • pp.2249-2252
    • /
    • 2011
  • Two new carborane complexes containing closo- or nido-carborane diphosphine ligands with the formula: complex $[Hg(7,8-(PPh_2)_2-7,8-C_2B_9H_{10})_2]$ $CH_2Cl_2$ (1) and $[Ag_2({\mu}-Cl)_2(1,2-(P^iPr_2)_2-1,2-C_2B_{10}H_{10})_2]$ (2) have been synthesized and characterized by elemental analysis, 1H and 13C NMR spectroscopy and X-ray structure determination. The X-ray structure analyses revealed that the carborane diphosphine ligand was degraded from closo-1,2-$(PPh_2)_2-1,2-C_2B_{10}H_{10}$ to nido-[$7,8-(PPh_2)_2-7,8-C_2B_9H_{10}]^-$ in complex 1, while the closo nature of the starting ligand $1,2-(P^iPr_2)_2-1,2-C_2B_{10}H_{10}$ was retained in complex 2. In either of the two complexes, the carborane diphosphine ligand was coordinated bidentately to the Hg(II) or Ag(I) center through its two phosphorus atoms, therefore forming a five-member cheating ring between the carborane ligand and the metal center. The coordination geometry of the metal atom is distorted tetrahedron formed by $P_4$ unit in complex 1 and $P_2Cl_2$ unit in complex 2, respectively.

Molecular Characterization and Phylogenetic Analysis of Season Influenza Virus Isolated in Busan during the 2006-2008 Seasons (부산지역에서 유행한 계절인플루엔자바이러스의 유전자 특성 및 계통분석('06-'08 절기))

  • Park, Yon-Koung;Kim, Nam-Ho;Choi, Seung-Hwa;Lee, Mi-Oak;Min, Sang-Kee;Kim, Seong-Joon;Cho, Kyung-Soon;Na, Young-Nan
    • Journal of Life Science
    • /
    • v.20 no.3
    • /
    • pp.365-373
    • /
    • 2010
  • To monitor newly emerged influenza virus variants and to investigate the prevalence pattern, our laboratory performed isolation of the viruses from surveillance sentinel hospitals. In the present study, we analysed influenza A/H1N1, A/H3N2, B viruses isolated in Busan during the 2006/07 and 2007/08 seasons by sequence analysis of the hemagglutinin (HA1 subunit) and neuraminidase (NA) genes. The isolates studied here were selected by the stratified random sample method from a total of 277 isolates, in which 15 were A/H1N1, 16 were A/H3N2 and 29 were B. Based on the phylogenetic tree, the HA1 gene showed that A/H1N1 isolates had a 96.7% to 97.7% homology with the A/Brisbane/59/2007, A/H3N2 isolates had a 98.4% to 99.7% homology with the A/Brisbane/10/2007, and B isolates had a 96.5% to 99.7% homology with the B/Florida/4/2006(Yamagata lineage), which are all the vaccine strains for the Northern Hemisphere in 2008~2009 season. In the case of the NA gene, A/H1N1 isolates had 97.8% to 98.5% homologies, A/H3N2 isolates had 98.9% to 99.4% homologies, and B isolates had 98.9% to 100% homologies with each vaccine strain in the 2008~2009 season, respectively. Characterization of the hemagglutinin gene revealed that amino acids at the receptor-binding site and N-linked glycosylation site were highly conserved. These results provide useful information for the control of influenza viruses in Busan and for a better understanding of vaccine strain selection.

Synthesis of Novel 6,7,8,9-Tetrahydro-5H-5-hydroxyphenyl-2-benzylidine-3-substituted Hydrazino Thiazolo (2,3-b) Quinazoline as Potent Antinociceptive and Anti-inflammatory Agents

  • Selvam, T. Panneer;Kumar, P. Vijayaraj
    • Bulletin of the Korean Chemical Society
    • /
    • v.31 no.11
    • /
    • pp.3265-3271
    • /
    • 2010
  • A series of 6,7,8,9-tetrahydro-5H-5-hydroxyphenyl-2-benzylidine-3-substituted hydrazino thiazolo (2,3-b) quinazolines have been synthesized to meet the structural requirements essential for anti-inflammatory and antinociceptive properties. The synthesized series of heterocycles, 6,7,8,9-tetrahydro-5H-5-hydroxyphenyl-2-benzylidine-3-substituted hydrazino thiazolo (2,3-b) quinazoline by the reaction of 6,7,8,9-tetrahydro-5H-5-hydroxy phenyl thiazolo (2,3-b) quinazolin-3(2H)-one with appropriate hydrazine hydrate and ketones/aldehydes in the presence of anhydrous sodium acetate and glacial acetic acid as presented in Scheme 1. Their antinociceptive activity were evaluated by tailflick technique, anti-inflammatory was evaluated by carrageenan-induced paw edema test and their ulcerogenicity index determined by reported protocol. The compounds exhibited the lowest ulcer index ($0.51{\pm}1.63$, $0.48{\pm}1.28$ and $0.50{\pm}1.53$, respectively. The 6,7,8,9-tetrahydro-5H-5-hydroxy phenylhydroxy-2-benzylidine-3-(N'-3-pentylidenehydrazino) thiazolo (2,3-b) quinazoline and 6,7,8,9-tetrahydro-5H-5-hydroxy phenyl-2-benzylidine-3-(N'-2-pentylidene-hydrazino) thiazolo (2,3-b) quinazoline exhibited the most potent antinociceptive and anti-inflammatory activities.

Constituents of the Herb of Isodon excisus var. coreanus

  • Kim, Ho-Kyoung;Whang, Wan-Kyunn;Kim, Il-Hyuk
    • Archives of Pharmacal Research
    • /
    • v.20 no.3
    • /
    • pp.291-296
    • /
    • 1997
  • The studies were carried out to evaluate the constituents in the aerial part of Isodon excisus var. coreanus (Labiatae). From the aqueous fraction of methanol extract, compound I (${\alpha}$-[[3-(3, 4-dihydroxyphenyl)-1-oxo-2-propenyl]oxy]-3,4-dihydroxy-benzenepropanoic acid), compound II (9-methyl-dihydroferulic acid-4-O-.betha.-D-glucopyranosyl $(1{\rightarrow}2)$-${\alpha}$-L- rhamnopyranosyl (1.rarw.4)-.betha.-D-glucopyranoside), compound III (ent-7.alpha., 11${\alpha}$,15.betha.-trihydroxy-kaur-16-en-1-O-.betha.-D-glucopyranoside) and compound IV ($2{\alpha}$,3${\beta}$,$7{\alpha}$,23-tetrahydroxy-olean-12 -en-28-oic acid 28-O-${\beta}$-D-glucopyranoside) were isolated and identified on the basis of their physicochemical and spectroscopic evidences[IR, FAB(-)MS,$^{1}H-NMR,$$^{13}C-NMR,$$ HMQC$$^{1}H-^{1}H $COSY and HMBC (Heteronuclear Multiple Bond Connectivity)]. Especially, New compounds II and III were named Isodonin A and Isodonin B respectively.

  • PDF

A Co-inhibitory Molecule, B7-H4, Synergistically Potentiates Oral Tolerance by Inducing CD4+CD25+FoxP3+ T Cells

  • Wen, Lanying;Yang, Sung-Yeun;Choi, Jae-Kyoung;Kim, Young-Hee;Kwon, Eun-Hee;Lee, Hyun-Ji;Jeoung, Hae-Young;Hwang, Du-Hyeon;Hwang, Dong-Jin;Choi, In-Hak
    • IMMUNE NETWORK
    • /
    • v.8 no.1
    • /
    • pp.21-28
    • /
    • 2008
  • Background: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. Methods: Balb/c $(H-2^d)$ mice were fed with dendritic cell line, DC2.4 $(H-2^d)$ every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. Results: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-${\gamma}$, IL-5, and TNF-${\alpha}$. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. Conclusion: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.