Interleukin-6 production in "normal" and HTLV-1 tax-expressing brain-specific endothelial cells.

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 Immunol

authors

Rott O,Tontsch U,Fleischer B,Cash E

doi

10.1002/eji.1830230839

subject

Has Abstract

pub_date

1993-08-01 00:00:00

pages

1987-91

issue

8

eissn

0014-2980

issn

1521-4141

journal_volume

23

pub_type

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