Abstract:
:Induction of the glucocorticoid-induced leucine zipper (GILZ) by glucocorticoids plays a role in their antiinflammatory action, whereas GILZ expression is reduced under inflammatory conditions. The mechanisms regulating GILZ expression during inflammation, however, have not yet been characterized. Here, we investigated GILZ expression in human alveolar macrophages (AMs) following Toll-like receptor (TLR) activation. Macrophages were shown to predominantly express GILZ transcript variant 2. Lipopolysaccharide-treated AMs, THP-1 cells, and lungs of lipopolysaccharide-exposed mice displayed decreased GILZ protein and mRNA levels. The effect was strictly dependent on the adapter molecule MyD88, as shown by using specific ligands or a knockdown strategy. Investigations on the functional significance of GILZ downregulation performed by GILZ knockdown revealed a proinflammatory response, as indicated by increased cytokine expression and NF-κB activity. We found that TLR activation reduced GILZ mRNA stability, which was mediated via the GILZ 3'-untranslated region. Finally, involvement of the mRNA-binding protein tristetraprolin (TTP) is suggested, since TTP overexpression or knockdown modulated GILZ expression and TTP was induced in a MyD88-dependent fashion. Taken together, our data show a MyD88- and TTP-dependent GILZ downreg-ulation in human macrophages upon TLR activation. Suppression of GILZ is mediated by mRNA destabilization, which might represent a regulatory mechanism in macrophage activation.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Hoppstädter J,Diesel B,Eifler LK,Schmid T,Brüne B,Kiemer AKdoi
10.1002/eji.201142081subject
Has Abstractpub_date
2012-05-01 00:00:00pages
1282-93issue
5eissn
0014-2980issn
1521-4141journal_volume
42pub_type
杂志文章abstract::Mature T cells first appear in the thymus of the mouse a few days before birth, about 7-8 days after the thymus was colonized by stem cells. These mature cells are exported to the peripheral lymphoid organs beginning at about the time of birth, but because the number is very small at this stage, little is known about ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220207
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abstract::Mast cells are important cellular constituents of epithelial-mesenchymal interactions, densely located at sites of microbial entry into the host where they are continuously exposed to products from commensals. In order to avoid excessive activation and the associated pathology, mast cell responses to TLR agonists must...
journal_title:European journal of immunology
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abstract::The DC-derived chemokine CCL17, a ligand of CCR4, has been shown to promote various inflammatory diseases such as atopic dermatitis, atherosclerosis, and inflammatory bowel disease. Under steady-state conditions, and even after systemic stimulation with LPS, CCL17 is not expressed in resident splenic DCs as opposed to...
journal_title:European journal of immunology
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abstract::DC-based vaccination against Leishmania major induces a parasite-specific Th1 response and long-lasting protective immunity in susceptible mice. Since distinct DC subsets have been proposed to direct the predominant development of either Th1 or Th2 cells, we analyzed the capability of plasmacytoid DC (pDC) to induce p...
journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2007-09-01 00:00:00
abstract::Hybrid virus-like particles (VLP) were prepared by self-assembly of the modified porcine parvovirus (PPV) VP2 capsid protein carrying a CD8+ or CD4+ T cell epitope. Immunization of mice with a single dose of these hybrid pseudo-particles, without adjuvant, induced strong cytotoxic T lymphocyte and T helper (Th) respon...
journal_title:European journal of immunology
pub_type: 杂志文章
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abstract::The immunosuppressor sanglifehrin A (SfA) is a member of a family of immunophilin cyclophilin A-binding molecules and does not inhibit calcineurin activity. Sanglifehrin A inhibits M-CSF-dependent macrophage proliferation by arresting the G1 phase of the cell cycle but does not affect cell viability. This immunosuppre...
journal_title:European journal of immunology
pub_type: 杂志文章
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abstract::The transforming protein of mouse polyomavirus, the mouse middle T antigen (MomT), and its counterpart in the hamster polyomavirus, the hamster middle T antigen (HamT), interact with a number of cellular proteins. Among these are members of the Src family of tyrosine kinases, the phosphatidylinositol 3-kinase, the ser...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250212
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abstract::The N-terminal amino acid sequence (26 residues) of a delta-chain of a human myeloma (Er I) is homologous with the prototype sequence of the human VHIII subgroup. This indicates that the delta-chain is using for its V region the same pool of V genes as the rest of the immunoglobulin classes. Implications of this findi...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830060315
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abstract::Stimulation of T cells via the T cell receptor (TCR) leads to an increase intracellular in free Ca2+ levels ([Ca2+]i) and the activation of the MAP kinase signaling pathway. This study analyzes for the first time Ca2+ fluxes in naive cytotoxic T cells stimulated with full agonists, partial agonists, or antagonists. Fo...
journal_title:European journal of immunology
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doi:10.1002/eji.1830271241
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830130602
更新日期:1983-06-01 00:00:00
abstract::The pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) have been shown to be primary mediators in the pathogenesis of chronic inflammatory joint diseases. However, the relative contributions of these molecules to the development and progression of disease is not known. In the present study...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250647
更新日期:1995-06-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200737395
更新日期:2008-03-01 00:00:00
abstract::A monoclonal antibody (12-15) reactive with the mouse CD2 was used to study the expression of the antigen in different lymphoid cell subsets. By two-color immunofluorescence using B or T cell-specific reagents and cell sorting in combination with biochemical analysis we provide evidence that the CD2 antigen is present...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830190826
更新日期:1989-08-01 00:00:00
abstract::Signal transducer and activator of transcription 3 (STAT3) triggered production of Th-17 cytokines mediates protective immunity against fungi. Mutations affecting the STAT3/interleukin 17 (IL-17) pathway cause selective susceptibility to fungal (Candida) infections, a hallmark of chronic mucocutaneous candidiasis (CMC...
journal_title:European journal of immunology
pub_type: 临床试验,杂志文章
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更新日期:2015-10-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830271004
更新日期:1997-10-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830201226
更新日期:1990-12-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830251118
更新日期:1995-11-01 00:00:00
abstract::Maintenance of peripheral tolerance and inactivation of autoreactive T cells is based on a delicate balance between pro-inflammatory and protective cytokines that is poorly understood. We have here addressed how the local expression of the inflammatory cytokine TNF-alpha can impair peripheral tolerance and lead to aut...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200323328
更新日期:2003-05-01 00:00:00
abstract::Alpha-galactosylceramide (alpha-GalCer) activates invariant (i)NKT cells, which in turn stimulate immunocompetent cells. Although activation of iNKT cells appears critical for regulation of immune responses, it remains elusive whether protection against intracellular bacteria can be induced by alpha-GalCer. Here, we s...
journal_title:European journal of immunology
pub_type: 杂志文章,收录出版
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abstract::Transcriptional up-regulation of the VCAM-1 gene, induced by proinflammatory cytokines such as IL-1beta and TNF-alpha, requires activation of not only NF-kappaB, but also involves interferon regulatory factor (IRF)-1. During a study of gene induction by mechanical stimuli in cultured human endothelial cells, we noted ...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830050803
更新日期:1975-08-01 00:00:00
abstract::A number of applications of antibodies in diagnosis and therapy require multivalent reagents either because of the polymeric nature of the antigens or because biological activity depends on an effect on the formation of homodimeric species. Here, we report a procedure for mass screening of phage-derived monomeric anti...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270307
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journal_title:European journal of immunology
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更新日期:2015-11-01 00:00:00
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:1978-04-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2007-08-01 00:00:00
abstract::Recent studies have shown that in humans the germinal center reactions produce three types of V(D)J mutated B cells in similar proportions, i.e. Ig-switched, IgD-IgM+ (IgM-only) and IgD+IgM+ cells, and that together they form the CD27+ compartment of recirculating B cells. We investigated the Ig isotype switch capacit...
journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00