Differential expression of toll-like receptor signaling cascades in LPS-tolerant human peripheral blood mononuclear cells

Differential expression of toll-like receptor signaling cascades in LPS-tolerant human peripheral blood mononuclear cells

Author Mendes, Marialice Erdelyi Autor UNIFESP Google Scholar
Baggio-Zappia, Giovana Lotici Autor UNIFESP Google Scholar
Colo Brunialti, Milena Karina Autor UNIFESP Google Scholar
Fernandes, Maria da Luz Autor UNIFESP Google Scholar
Rapozo, Marjorie Marini Autor UNIFESP Google Scholar
Salomao, Reinaldo Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Pre-exposure to low doses of LPS induces resistance to a lethal challenge, a phenomenon known as endotoxin tolerance. in this study, tolerance was induced in human PBMC by culturing cells with 1 ng/mL LPS for 48 h. Cells were subsequently challenged with 100 ng/mL LPS for 2, 6 and 24 h, and the expression of 84 genes encoding proteins involved in the TLR signaling pathway was evaluated at each time point by PCR array. LPS pretreatment did not modulate the expression of TLR4 and CD14 on the surface of monocytes. A gene was defined as tolerized when LPS pretreatment reversed the effect of LPS challenge on the expression of the gene or as non-tolerized when LPS pretreatment did not reverse the effects of LPS challenge. We observed impaired signal transduction through the NF-kappa B, JNK, ERK and TRIF pathways, whereas expression of p38 pathway-related genes was preserved in LPS-tolerant cells. These results show a distinct regulation of the TLR pathway cascades during tolerance; this may account for the differential gene expression of some inflammatory mediators, such as up-regulation of IL-10 and COX2 as well as down-regulation of INF-alpha and IL-12. Depending on the effect of LPS-induced gene up-regulation or down-regulation, tolerance, as a reversion of such LPS effects, may result in repression or induction of gene expression. (C) 2010 Elsevier GmbH. All rights reserved.
Keywords Gene expression
Innate immunity
LPS
p38
PBMC
Tolerance
Toll-like receptors
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2006/58744-1
FAPESP: 2007/56960-7
Date 2011-03-01
Published in Immunobiology. Jena: Elsevier Gmbh, Urban & Fischer Verlag, v. 216, n. 3, p. 285-295, 2011.
ISSN 0171-2985 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 285-295
Origin http://dx.doi.org/10.1016/j.imbio.2010.07.008
Access rights Closed access
Type Article
Web of Science ID WOS:000288722500002
URI http://repositorio.unifesp.br/handle/11600/33525

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