共查询到20条相似文献,搜索用时 484 毫秒
1.
Jurka J 《Cellular and molecular life sciences : CMLS》2008,65(2):201-204
Multiple remnants of transposable elements preserved in cis-regulatory modules may represent a record of mutations that were critical to the evolution of gene regulation and speciation.
Received 13 August 2007; received after revision 8 October 2007; accepted 23 October 2007 相似文献
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Jin-ichi Inokuchi Masakazu Nagafuku Isao Ohno Akemi Suzuki 《Cellular and molecular life sciences : CMLS》2013,70(17):3067-3075
Gangliosides are major components of highly organized membrane microdomains or rafts, yet little is known about the role of gangliosides in raft organization. This is also the case of gangliosides in TCR-mediated activation. Comprehensive structural analysis of gangliosides in the primary thymocytes and CD4+ T and CD8+ T cells was not achieved due to technical difficulties. We have found that CD8+ T cells express very high levels of o-series gangliosides, but on the other hand, CD4+ T cells preferably express a-series gangliosides. In the TCR-dependent activation, CD4+ T cells selectively require a-series gangliosides, but CD8+ T cells do require only o-series gangliosides but not a-series gangliosides. Ganglioside GM3 synthase-deficient mice lacking a-series gangliosides neither exhibited the TCR-dependent activation of CD4+ T nor developed ovalbumin-induced allergic airway inflammation. These findings imply that the distinct expression pattern of ganglioside species in CD4+ and CD8+ T cells define the immune function of each T cell subset. 相似文献
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HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains 总被引:4,自引:0,他引:4
Jiang JL Chan HC Zhou Q Yu MK Yao XY Lam SY Zhu H Ho LS Leung KM Chen ZN 《Cellular and molecular life sciences : CMLS》2004,61(16):2083-2091
HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca2+ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca2+ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721C and T7721N cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721C cells, but not affected in T7721N cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca2+ mobilization although each domain may play different roles.Received 1 April 2004; received after revision 15 June 2004; accepted 22 June 2004 相似文献
5.
Chopra VS 《Cellular and molecular life sciences : CMLS》2011,68(6):977-990
Metazoan genomes primarily consist of non-coding DNA in comparison to coding regions. Non-coding fraction of the genome contains
cis-regulatory elements, which ensure that the genetic code is read properly at the right time and space during development.
Regulatory elements and their target genes define functional landscapes within the genome, and some developmentally important
genes evolve by keeping the genes involved in specification of common organs/tissues in clusters and are termed gene complex.
The clustering of genes involved in a common function may help in robust spatio-temporal gene expression. Gene complexes are
often found to be evolutionarily conserved, and the classic example is the hox complex. The evolutionary constraints seen
among gene complexes provide an ideal model system to understand cis and trans-regulation of gene function. This review will discuss the various characteristics of gene regulatory modules found within
gene complexes and how they can be characterized. 相似文献
6.
Naïve CD4+ T cells undergo massive cell proliferation upon encountering their cognate ligand. This proliferation depends upon appropriate cues from the antigen-presenting cells that have processed the antigen and present the peptide to the T cells, and requires the establishment of a cytokine environment that can support such proliferation. Expansion of antigen-specific CD4+ T cells needs to be coupled with differentiation into one of several effector/regulatory phenotypes if the priming event is to result in cells that can initially act to control the particular pathogen that elicited the response, and later to serve as memory cells to insure an appropriate response upon reintroduction of the pathogen. Here, we discuss the initiation of T helper lineage commitment, the positive feedback regulation by the cytokine environment to enhance and stabilize the differentiation into distinct T helper subsets, and the biological significance of CD4+ T cell plasticity and long-term CD4+ T cell memory. 相似文献
7.
Wittkopp PJ 《Cellular and molecular life sciences : CMLS》2005,62(16):1779-1783
Regulatory variation results from genetic changes with both cis and trans acting effects on gene expression. Here I describe the types of genetic variants that alter cis and trans regulation and discuss differences in the potential for cis and trans changes among different classes of genes. I argue that the molecular function of the protein encoded by each gene and how the gene is wired into the genomic regulatory network may influence its propensity for cis and trans regulatory changes.Received 15 February 2005; received after revision 12 April 2005; accepted 26 April 2005 相似文献
8.
Major contribution of codominant CD8 and CD4 T cell epitopes to the human cytomegalovirus-specific T cell repertoire 总被引:3,自引:0,他引:3
Nastke MD Herrgen L Walter S Wernet D Rammensee HG Stevanović S 《Cellular and molecular life sciences : CMLS》2005,62(1):77-86
Human cytomegalovirus (HCMV) infection or reactivation is a cause of morbidity and mortality in immunocompromised individuals. In immunocompetent individuals, in contrast, HCMV is successfully controlled by specific CD8 and CD4 T cells. Knowledge of CD8 and CD4 T cell epitopes from HCMV and their immunodominant features is crucial for the generation of epitope-specific T cells for adoptive immunotherapy and for the development of a peptide-based HCMV vaccine. Therefore, we investigated the natural frequencies of a large number of CD8 and CD4 T cell epitopes, including 10 novel ones. We determined several epitopes as immunodominant. Surprisingly, no clear hierarchies were found for CD8 T cell epitopes, indicating codominance. These results will be valuable for adoptive transfer strategies and support initiatives towards development of a peptide-based HCMV vaccine.Received 12 August 2004; received after revision 24 September 2004; accepted 29 October 2004 These authors contributed equally to this work. 相似文献
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Cytotoxic (CD8+) and helper (CD4+) T cells play a crucial role in resolving infections by intracellular pathogens. The development of technologies to visualize
antigen-specific T cell responses in mice and men over the past decade has allowed a dissection of the formation of adaptive
T cell immunity. This review gives a brief overview of the currently used detection techniques and possible future additions.
Furthermore, we discuss our current understanding of the formation of antigen-specific T cell responses, with particular attention
to the similarities and differences in CD4+ and CD8+ T cell responses, the functional heterogeneity within responder T cell pools and the regulation of CD8+ T cell responses by dendritic cells and CD4+ helper T cells.
Received 16 June 2005; received after revision 2 August 2005; accepted 15 August 2005 相似文献
11.
Fu WX Gong SY Qian XP Li Y Zhu ML Dong XY Li Y Chen WF 《Cellular and molecular life sciences : CMLS》2004,61(15):1935-1945
Mouse platelet basic protein (CXCL7/mPBP) was cloned from thymic stromal cells and further identification
indicated that it was expressed in thymic monocytes/macrophages (Mo/Ms). Recombinant mPBP was
chemoattractive for target cells of polymorphonuclear leucocytes, peritoneal Mo/Ms and splenic lymphocytes
with distinct potencies. CXCR2 was identified to be a cognate receptor for mPBP. Mouse thymocyte subsets of
CD4-CD8- double-negative (DN),
CD4+CD8+ double-positive (DP),
CD4+CD8- single-positive (CD4SP)
and CD4-CD8+ single-positive (CD8SP) expressed cell surface
CXCR2 with different positive percentages and expression levels. mPBP was chemoattractive for thymocyte subsets
with the potency order DN>DP> CD8SP>CD4SP, consistent with the levels of CXCR2 expressed on the
respective cells. Thus, mPBP in thymus is functionally redundant with chemokine CXCL12/ SDF-1. Moreover, our
finding that thymic Mo/Ms can produce mPBP implies that they may have other functions apart from acting as
scavengers in thymus.Received 25 March 2004; received after revision 10 May 2004; accepted 8 June 2004 相似文献
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Forkhead transcription factors in immunology 总被引:5,自引:0,他引:5
14.
Diana Rita Szabó Kornélia Baghy Peter M. Szabó Adrienn Zsippai István Marczell Zoltán Nagy Vivien Varga Katalin Éder Sára Tóth Edit I. Buzás András Falus Ilona Kovalszky Attila Patócs Károly Rácz Peter Igaz 《Cellular and molecular life sciences : CMLS》2014,71(5):917-932
The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentration- and time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer. 相似文献
15.
Lei Chen Cong-Fa Huang Yi-Cun Li Wei-Wei Deng Liang Mao Lei Wu Wen-Feng Zhang Lu Zhang Zhi-Jun Sun 《Cellular and molecular life sciences : CMLS》2018,75(11):2045-2058
The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1β production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4+ and CD8+ T cells in HNSCC mice. Notably, the numbers of exhausted PD-1+ and Tim3+ T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1β pathway may provide a novel approach for HNSCC therapy. 相似文献
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T cell activation is enhanced by the costimulatory interaction of B7 on antigen-presenting cells and CD28 on T cells, resulting
in long-term T cell proliferation, differentiation and production of large amounts of cytokines, such as interleukin (IL)-2.
CTLA-4 is a co-stimulation receptor that shares 31% homology with CD28 and binds B7 family members with higher affinity. CTLA-4
is transiently expressed intracellularly and on the cell surface following activation of T cells. We have studied the kinetics
of CTLA-4 expression and the effects of dexamethasone on CTLA-4 expression during T cell activation in cultures of mouse spleen
cells stimulated by a mixture of immobilized anti-CD3 and anti-CD28 monoclonal antibodies (anti-CD3/CD28 mAb) or concanavalin
A (ConA). CTLA-4 expression peaked on day 2 and returned to background levels after 7 days. Dexamethasone was found to potentiate
CTLA-4 expression in a dose-dependent manner with an EC50 effective concentration 50%) of about 10−8 M. In contrast, other immunosuppressive agents, such as rapamycin or cyclosporin A had no or an inhibitory effect on CTLA-4
expression, respectively. Dexamethasone also stimulated CD28 expression, but inhibited IL-2R expression during anti-CD3/CD28
mAb-induced mouse splenic T cell activation. Western blot analyses of lysates of activated mouse T cells showed that dexamethasone
increased CTLA-4 protein levels twofold during anti-CD3/CD28 mAb-induced activation. Dexamethasone also enhanced CTLA-4 messenger
RNA twofold as quantified by ribonuclease protection assay. The effects of dexamethasone on CTLA-4 expression were glucocorticoid-specific
and completely inhibited by the glucocorticoid receptor antagonist mifepristone (RU486), indicating that the effect of dexamethasone
on CTLA-4 expression is mediated through the glucocorticoid receptor. In conclusion, the immunosuppressive agent dexamethasone
actually stimulates CTLA-4 expression, which is involved in downregulation of T cell activation.
Received 19 May 1999; received after revision 13 July 1999; accepted 13 July 1999 相似文献
18.
High frequency of human cytomegalovirus (HCMV)-specific CD8+-T cells detected in a healthy CMV-seropositive donor 总被引:2,自引:0,他引:2
Lang KS Moris A Gouttefangeas C Walter S Teichgräber V Miller M Wernet D Hamprecht K Rammensee HG Stevanovic S 《Cellular and molecular life sciences : CMLS》2002,59(6):1076-1080
Human cytomegalovirus (HCMV) persists after infection but is controlled by cellular immune responses, particularly by CD8+ T cells. If infected individuals are immunosuppressed, HCMV can be reactivated. Upon testing the blood of healthy donors
with human lymphocyte antigen tetramers, we found one individual with about 50 % of his CD8+ T cells being specific for the immunodominant pp65 epitope NLVPMVATV. Over a period of 2 years the high level of HCMV-specific
T cells was maintained, and no HCMV DNA could be detected. At one timepoint, however, HCMV-specific DNA was detected, while
65 % of CD8+ T cells were specific for HCMV. When virus was detectable, a lower percentage of HCMV-specific CD8+ T cells showed interferon γ (IFN-γ) production after peptide stimulation in vitro. These data suggest that HCMV reactivation
may also occur in immunocompetent persons, accompanied by the presence of HCMV-specific CD8+ T cells which are not producing IFNγ, and therefore potentially anergic or in vivo exhausted.
Received 6 March 2002; received after revision 15 April 2002; accepted 17 April 2002 相似文献
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CD100 is a leukocyte semaphorin 总被引:5,自引:0,他引:5
S. Delaire A. Elhabazi A. Bensussan L. Boumsell 《Cellular and molecular life sciences : CMLS》1998,54(11):1265-1276
CD100 was originally described as an activation molecule on the surface of human T lymphocytes. Its triggering through distinct
epitopes leads to different signals of costimulation with phorbol myristate acetate (PMA) or with CD3 and CD2. Interestingly,
CD100 was shown to associate with different partner molecules in T cells. First, CD100 can associate with CD45, a key molecule
with protein tyrosine phosphatase activity involved in T-cell transduction this association is physical and has functional
consequences for both partners. Second, CD100 interacts in its cytoplasmic domain with a Ser/Thr kinase for which it represents
a preferential substrate. Recently, CD100 was identified as a member of the semaphorin gene family. This family comprises
approximately 20 structurally related proteins. The first semaphorins were identified in the developing nervous system. Function
has been shown for only some of them and involves repulsion during growth cone guidance. Since CD100 was the first semaphorin
identified in the immune system, this raises the possibility of the involvement of members of the semaphorin family in other
physiological phenomena outside the nervous system.
Received 1 March 1998; received after revision 8 June 1998; accepted 8 June 1998 相似文献