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TNF reduces LIF endocytosis despite increasing NFκB‐mediated gp130 expression
Author(s) -
Yu Chuanhui,
Kastin Abba J.,
Pan Weihong
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21105
Subject(s) - proinflammatory cytokine , glycoprotein 130 , tumor necrosis factor alpha , cytokine , leukemia inhibitory factor , downregulation and upregulation , endocytosis , microbiology and biotechnology , receptor , chemistry , biology , stat3 , signal transduction , cancer research , endocrinology , interleukin 6 , immunology , inflammation , biochemistry , gene
To examine how the proinflammatory cytokine tumor necrosis factor α (TNF) modulates the response of cerebral microvessels to other cytokines, we used rat cerebral microvessel endothelial RBE4 cells to simulate the in vitro blood‐brain barrier (BBB). The gp130 receptor, which is shared by the interleukin (IL)‐6 family of cytokines, showed specific upregulation by TNF. TNF treatment (5 ng/ml for 30 min to 24 h) increased gp130 at both the levels of transcription and protein expression. The stability of gp130 protein was mediated by NFκB activity, as the inhibitors quinazoline and MG132 not only blocked the increase induced by 6 h of TNF treatment, but also reduced its basal level of expression. By contrast, the lysosomal inhibitor chloroquine and the extracellular regulated kinase inhibitor U0126 showed no effect. Despite the increase of gp130, TNF caused a significant reduction in the cell binding and endocytosis of leukemia inhibitory factor (LIF), another proinflammatory cytokine that binds to the gp130 co‐receptor and its unique gp190 receptor. This is consistent with our previous findings that TNF reduces gp190 expression and Stat3 activation. Thus, TNF stimulation results in decreased responsiveness of RBE4 cells to LIF, indicating complex regulatory interactions of cytokines at the BBB. J. Cell. Physiol. 213: 161–166, 2007. © 2007 Wiley‐Liss, Inc.