Abstract:
:The extracellular signal-regulated kinase (ERK) signaling pathway is strongly activated in response to TCR stimulation in normal T cells. However, the extent to which activation of the ERK pathway is necessary for TCR-stimulated cytokine production is not clear. We have addressed this question by use of two separate methods to interfere with TCR activation of the ERK cascade. The first approach utilized transient expression of a catalytically inactive form of mitogen-activated/ERK 1 (CI-MEK1), while the second involved using the MEK1- and MEK2-specific inhibitor PD98059 to block ERK activation by the TCR. In order to assess the requirement for ERK activation in T cell cytokine production, we have measured the effect of ERK inhibition upon the production of six cytokines, IL-3, IL-4, IL-5, IL-10, granulocyte macrophage colony stimulating factor (GM-CSF) and IFN-gamma, by newly activated normal mouse T cells in response to TCR stimulation. The results of experiments using both methods to block ERK activation have revealed a requirement for intact ERK signaling for the full elicitation of TCR-stimulated cytokine production. Dose-response analyses using the MEK inhibitor PD98059 showed that the TCR-stimulated production of all cytokines measured was affected by this treatment. However, the production of IL-3 and IL-4 was only partially dependent upon ERK activation, whereas IL-5, IL-10, IFN-gamma and GM-CSF production was severely affected by diminished ERK activation. We conclude that the ERK pathway is differentially involved in the activation of different cytokine genes in normal T cells.
journal_name
Int Immunoljournal_title
International immunologyauthors
Egerton M,Fitzpatrick DR,Kelso Adoi
10.1093/intimm/10.2.223subject
Has Abstractpub_date
1998-02-01 00:00:00pages
223-9issue
2eissn
0953-8178issn
1460-2377journal_volume
10pub_type
杂志文章abstract::Auto-antibodies against heat shock proteins (HSPs) are frequently found in the sera of patients with rheumatic and other autoimmune diseases. However, it is unclear whether these auto-antibodies play a role in the pathophysiology and etiology of these diseases. We found that a murine anti-HSP60 mAb enhanced the produc...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh399
更新日期:2006-04-01 00:00:00
abstract::Organs of transgenic pigs that express human complement regulatory proteins are under assessment as an alternative to transplantation. A major barrier to the transplantation of pig organs is the hyperacute rejection caused by pre-existing antibodies and complement. Pig cells are very susceptible to human complement, p...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.6.869
更新日期:1997-06-01 00:00:00
abstract::It is increasingly evident that neutrophils are able to cross-talk with other leukocytes to shape ongoing inflammatory and immune responses. In this study, we analyzed whether human NK cells may influence the survival and activation of neutrophils under co-culture conditions. We report that NK cells exposed to either ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq434
更新日期:2010-10-01 00:00:00
abstract::The TCR is responsible for the specificity of cytotoxic T lymphocytes (CTL) by recognizing peptides presented in the context of MHC. By producing recombinant soluble TCR, it is possible to study this interaction at the molecular level. We generated single-chain TCR (scTCR) from tumor infiltrating lymphocytes (TIL) and...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.5.745
更新日期:1999-05-01 00:00:00
abstract::We have previously cloned the murine homolog of cDNA for the human myelomonocytic differentiation antigen, CD14. We synthesized three hydrophilic peptides derived from the predicted amino acid sequence of murine CD14 (mCD14), designated MS7.1, MS7.2, and MS7.3, respectively, and raised antisera against them. Each anti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.2.205
更新日期:1991-02-01 00:00:00
abstract::Antibody responses to ingested antigens can be inhibited by a mechanism known as oral tolerance which acts to prevent excessive stimulation from luminal contents. Local IgA responses can be induced in this non-responsive environment and during intestinal inflammation, mucosal IgG responses can also be increased. The p...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.9.975
更新日期:1992-09-01 00:00:00
abstract::Mercury-induced autoimmunity is characterized by a T cell-dependent B cell activation (mainly of IgG1 and IgE isotypes), production of anti-nucleolar autoantibodies (ANolA) and the formation of renal IgG deposits. The autoimmunity is to a large extent controlled by genetic factors. We studied 15 different inbred mouse...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.10.1425
更新日期:2000-10-01 00:00:00
abstract::Rheumatic fever (RF) follows a throat infection with different M-serotypes of beta-hemolytic group A streptococci (GAS) and can affect different tissues, predominantly the heart. It is thought to be an autoimmune illness. Although histological examination of affected heart shows an infiltrate consisting mainly of T ce...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.8.1235
更新日期:1994-08-01 00:00:00
abstract::The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A(+) cells play a role in this disease. Although elevated number of CD4(+) IL-17A(+) (Th17) and IL-17A(+)TCRγδ(+) T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv068
更新日期:2016-05-01 00:00:00
abstract::Recent studies have suggested that Fas-mediated apoptosis is involved in the pathogenesis of intestinal injury. In this study, we determined the role of Fas/Fas ligand (FasL) interactions in different T cell compartments using a murine model of small intestinal injury. An intraperitoneal injection of 145-2C11 (anti-CD...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh231
更新日期:2005-05-01 00:00:00
abstract::The ability of Bcl-2 to inhibit apoptotic cell death is well established. Several homologues of the bcl-2 gene, such as bax, bcl-x or mcl-1, have recently been identified. Like Bcl-2, both Bcl-XL and Mcl-1 appear to function as repressors of apoptotic cell death, whereas Bax facilitates it, indicating possible interac...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.11.1817
更新日期:1995-11-01 00:00:00
abstract::Dendritic cells (DC) are highly potent activators of the immune response. The precise mechanisms that give rise to the DC phenotype are not known. To investigate the mechanisms that contribute to the generation of the DC phenotype, precursor DC were freshly isolated from human blood and allowed to mature in vitro. The...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.11.1713
更新日期:1998-11-01 00:00:00
abstract::LPS-binding protein (LBP) can facilitate the transfer of cell wall components of both Gram-negative bacteria (LPS) and Gram-positive bacteria (lipoteichoic acid) to inflammatory cells. Although LBP is predominantly produced in the liver, recent studies have indicated that this protein is also synthesized locally in th...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh161
更新日期:2004-11-01 00:00:00
abstract::IFN-regulatory factor (IRF)-4 is a member of the IRF family of transcription factors expressed in lymphocytes and macrophages. The previous studies using mice deficient in the IRF-4 gene showed profound defects in function of both B and T cells. To further investigate the role of IRF-4 in CD4(+) T cell function, IRF-4...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg001
更新日期:2003-01-01 00:00:00
abstract::Activated macrophages exert strong arginase (ASE) activity that converts L-arginine into ornithine, the key precursor for putrescine and polyamine biosynthesis. Macrophages were previously also shown to generate nitric oxide that is derived from the guanido group of arginine by the oxidative deiminase (OAD) reaction. ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.5.413
更新日期:1991-05-01 00:00:00
abstract::The human IL-3 gene, located on chromosome 5, contains several cis-acting DNA sequences, i.e. CLE (conserved lymphokine element) and a GC-rich region, similar to the GM-CSF gene. To investigate the role of these elements, the 5' flanking region of the IL-3 gene was attached to a bacterial chloramphenicol acetyltransfe...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/3.3.245
更新日期:1991-03-01 00:00:00
abstract::Novel biomarkers of rheumatoid arthritis (RA), in addition to antibodies against cyclic citrullinated peptides, are required. Metabolome analysis is a promising approach to identify metabolite biomarkers for clinical diagnosis. We adopted a comprehensive nontargeted metabolomics approach combining capillary electropho...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxaa059
更新日期:2020-08-31 00:00:00
abstract::HLA-G, a human MHC class I molecule expressed on the trophoblast during pregnancy, was expressed in transgenic mice by recombining the HLA-G gene with a transcriptional promoter from a murine H-2 MHC class I gene. Skin grafts from HLA-G transgenic mice were rejected by non-transgenic mice showing that HLA-G behaves as...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.5.645
更新日期:1997-05-01 00:00:00
abstract::Heat shock protein (Hsp) 60 is thought to function as endogenous danger signal by activating professional antigen-presenting cells (APC) through toll-like receptor (TLR) 4 and CD14, a mechanism that is also used by bacterial LPS. We recently showed that Hsp60 binds LPS and enhances LPS-induced immune stimulation. On t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn003
更新日期:2008-03-01 00:00:00
abstract::Two peptides based on the complementarity-determining regions (CDR) 1 and 3 (pCDR1 and pCDR3) of a murine monoclonal anti-DNA autoantibody that expresses the common idiotype 16/6Id were shown to down-regulate systemic lupus erythematosus (SLE)-associated T cell responses and to prevent the development of clinical symp...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg026
更新日期:2003-02-01 00:00:00
abstract::Immunopathology and immune responses to Schistosoma mansoni were examined in IL-4 -/- mice. IL-5 and IL-10 production by lymphoid cells stimulated with soluble egg antigen (SEA), peripheral eosinophilia and serum levels of soluble IL-4 receptor but not IgE were all significantly elevated over background normal levels ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.4.435
更新日期:1996-04-01 00:00:00
abstract::The ability of cytokines to steer CD4(+) T(h) cell responses toward a T(h)1 or T(h)2 phenotype and enhance the magnitude of both CD8(+) cytotoxic T lymphocytes (CTL) and antibody responses has clearly been demonstrated by our lab and others, but the influence of cytokines on protective immune responses is much less cl...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/13.7.897
更新日期:2001-07-01 00:00:00
abstract::Secretory IgA (sIgA) antibodies in human tears and milk were found to recognize protein disulfide isomerase (PDI) on a Toxoplasma gondii lysate immunoblot (IB). These antibodies were already detectable in tears of infants. To determine the epitope containing-regions on PDI, we generated truncated versions of recombina...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxf091
更新日期:2002-11-01 00:00:00
abstract::Lymphocyte migration from the blood into specific tissues is directed by their expression of adhesion molecules referred to as homing receptors. The homing receptor L-selectin, for example, directs the migration of lymphocytes into peripheral lymph nodes (PLN). Since bovine gamma delta T cells, a major lymphocyte subs...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.1.81
更新日期:1994-01-01 00:00:00
abstract::Non-obese diabetic (NOD) mice that are genetically deficient in either IFN-gamma or beta chain of the IFN-gammaR develop diabetes with similar kinetics to wild-type NOD mice. In the current study, we demonstrated that treatment of IFN-gamma signaling-deficient NOD mice with cyclophosphamide (CY) not only fails to indu...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn080
更新日期:2008-09-01 00:00:00
abstract::Recent studies point to glycolipid-enriched membrane (GEM) microdomains as the critical sites for TCR-mediated signal transduction. However, whether the TCR complex is localized in the GEM domain is not well-defined. In the present study, we analyzed localization of the TCR-CD3 complex in the GEM domain by isolating t...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.9.1395
更新日期:1999-09-01 00:00:00
abstract::CT1 is a carbohydrate moiety of CD45 that is expressed on fetal thymocytes in vivo. Examination of CT1 expression on thymocyte subsets revealed that primarily pro-T cells (CD44+ CD25+) and pre-T cells (CD44- CD25+) expressed CT1. Interestingly, non-T-lineage committed lymphoid progenitors (CD44+ CD25-) lacked CT1 indi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.4.445
更新日期:1998-04-01 00:00:00
abstract::A canonical pre-TCR/TCR signaling pathway critical for thymic T cell development involves sequential phosphorylation and signaling through Lck, Zap70, Lat and Slp76. However, we and others have previously reported that genomic deletion of c-Cbl (Cbl) partially or completely reverses the defects in thymic development i...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxu105
更新日期:2015-05-01 00:00:00
abstract::Murine bone marrow-derived macrophages (BMM) are able to inhibit the intracellular growth of Mycobacterium bovis and Mycobacterium tuberculosis H37Rv after activation with recombinant (r) IFN and growth inhibition is mediated by reactive nitrogen intermediates (RNI) derived from L-arginine. We now demonstrate that tum...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.5.693
更新日期:1994-05-01 00:00:00
abstract::Antigen-coupled antigen-presenting cells (APC) serve as potent tolerogens for inhibiting immune responses in vivo and in vitro, apparently by providing an antigen-specific signal through the TCR in the absence of co-stimulation. Although this approach has been well studied in rodents, little is known about its effects...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.1.57
更新日期:2000-01-01 00:00:00