Abstract:
:Abnormal cytokine production can contribute in many instances to the development of pathology. Our study focuses on the regulation of interleukin (IL)-6 production in vitro in brain-specific endothelial cells (BEC) under physiological conditions and in a model of human T leukemia virus-1 (HTLV-1) infection. IL-6 production was strongly up-regulated in a dose-dependent mode upon exposure to recombinant IL-1 beta, although nearly not detectable in unstimulated BEC. This induction of IL-6 production could be achieved by reagents known to increase intracellular levels of cAMP, such as forskolin, prostaglandin E or pentoxifylline. Furthermore, transcription and production of IL-6 was inducible by addition of dibutyryl cAMP, but not by addition of calcium ionophores or diacylglycerol. To assess a potential role of HTLV-1-infected BEC in the pathogenesis of tropical spastic paraparesis (TSP), the HTLV-1 tax gene was expressed in BEC. Tax gene-expressing BEC produced constitutively very high amounts of IL-6, which were not longer hyperinducible by IL-1 beta or cAMP derivatives. Our results indicate that HTLV-1 tax induces hyperproduction of IL-6 in brain-specific endothelial cells directly by an intracellular mechanism which subsequently renders IL-6 production independent of exogenous stimuli or activators of (cAMP-dependent) second messenger levels. On the basis of these findings we suggest that tax-mediated hyperactivation of IL-6 production in BEC contributes to elevated IL-6 levels found in serum and cerebrospinal fluid of patients with TSP and might have a significance in the immune pathogenesis of the disease.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Rott O,Tontsch U,Fleischer B,Cash Edoi
10.1002/eji.1830230839subject
Has Abstractpub_date
1993-08-01 00:00:00pages
1987-91issue
8eissn
0014-2980issn
1521-4141journal_volume
23pub_type
杂志文章abstract::We have previously shown, through transfection experiments, that the murine B7 (mB7) molecule, a ligand for the CD28 and CTLA-4 receptors, is a sufficient costimulatory signal for the antigen-specific and major histocompatibility complex (MHC)-restricted activation of murine CD4+ T lymphocytes. In addition to mB7, ano...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830160412
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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.1830271231
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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:2000-01-01 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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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
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200007)30:7<1813::AID-IMMU1813>3
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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
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更新日期:1986-10-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270726
更新日期:1997-07-01 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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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:1984-06-01 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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更新日期:1987-02-01 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:2002-07-01 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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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
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journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:1985-07-01 00:00:00