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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Mendes, Marialice Erdelyi [1] ; Baggio-Zappia, Giovana Lotici [1] ; Colo Brunialti, Milena Karina [1] ; Fernandes, Maria da Luz [1] ; Rapozo, Marjorie Marini [1] ; Salomao, Reinaldo [1]
Total Authors: 6
Affiliation:
[1] Univ Fed Sao Paulo, Div Infect Dis, Escola Paulista Med, Dept Med, BR-04039032 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Immunobiology; v. 216, n. 3, p. 285-295, MAR 2011.
Web of Science Citations: 23
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. (AU)

FAPESP's process: 06/58744-1 - Sepsis: integrating basic research and clinical investigation
Grantee:Reinaldo Salomão
Support Opportunities: Research Projects - Thematic Grants