Abstract:
:Stimulation of human peripheral blood lymphocytes via T cell receptor/CD3 complex resulted in a bimodal activation of protein kinase(s) C (PKC). Within 10 min of stimulation PKC-alpha was translocated to, and thus activated in, the plasma membranes of human lymphocytes, followed by a fast dissociation of this isotype from the plasma membrane. This short term activation and translocation PKC-alpha proved to be cyclosporin A (CsA) insensitive. After 90 min of stimulation PKC-beta was translocated to and remained bound to the plasma membranes for up to 4 h. Preincubation of human lymphocytes with 200 ng/ml CsA specifically and completely abolished the sustained activation of PKC-beta. Neither the phorbol ester-induced direct activation of PKC nor the specific activity of the plasma membrane-bound enzyme was influenced by CsA, suggesting that a signal transduction pathway leading to sustained activation of PKC-beta was influenced by the immunosuppressive agent. In fact, CsA inhibited, in a concentration-dependent manner, the activation of lysophosphatid acyltransferase-catalyzed elevated incorporation of cis-polyunsaturated fatty acids into plasma membrane phospholipids. While interleukin-2 (IL-2) synthesis and cellular proliferation were completely inhibited by 200 ng/ml CsA in BMA 030- or BMA 031-stimulated cells, expression of high-affinity IL-2 receptors was not influenced by the immunosuppressive drug. These results suggest that synthesis and expression of high-affinity IL-2 receptors might be regulated by a signal-transducing pathway involving activation and translocation of PKC-alpha. Lysophosphatid acyltransferase-catalyzed incorporation of cis-polyunsaturated fatty acids might represent another mechanism of signal transduction implicated in the activation and translocation of PKC-beta, which is specifically inhibited by CsA. Neutralization of PKC-beta by introducing anti-PKC-beta antibodies prevented IL-2 synthesis and proliferation in stimulated human lymphocytes. The results suggest a possible link between activation of PKC-beta and regulation of IL-2 synthesis in activated human lymphocytes. Thus, inhibition of the activation and translocation of PKC-beta by CsA may result in inhibition of IL-2 gene expression in human lymphocytes.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Szamel M,Bartels F,Resch Kdoi
10.1002/eji.1830231205subject
Has Abstractpub_date
1993-12-01 00:00:00pages
3072-81issue
12eissn
0014-2980issn
1521-4141journal_volume
23pub_type
杂志文章abstract::By means of a novel technique for identification and isolation of MHC class II-restricted antigen-specific T cells, we describe here in non-transgenic BALB / c mice physiological positive selection of an oligoclonal population of T cells which recognizes both a self MHC-derived peptide (Ialpha52) and a bacterial homol...
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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更新日期:1991-03-01 00:00:00
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journal_title:European journal of immunology
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doi:10.1002/eji.1830230239
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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更新日期:1994-12-01 00:00:00
abstract::IL-7 is a major regulator of lymphocyte homeostasis; however, little is known about the mechanisms that regulate IL-7 production. To study Il7 gene regulation in vivo, we generated a novel IL-7-reporter mouse, which allows the non-invasive quantification of Il7 gene activity in live mice and, additionally, the simulta...
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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doi:10.1002/eji.1830210240
更新日期:1991-02-01 00:00:00
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journal_title:European journal of immunology
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doi:10.1002/eji.201142231
更新日期:2012-02-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830240828
更新日期:1994-08-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220324
更新日期:1992-03-01 00:00:00
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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更新日期:1998-02-01 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:1997-05-01 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:1999-04-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830071016
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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更新日期:1987-06-01 00:00:00
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journal_title:European journal of immunology
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更新日期:2005-03-01 00:00:00
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journal_title:European journal of immunology
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更新日期:2000-02-01 00:00:00