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Anti-inflammatory cytokines induce lipopolysaccharide tolerance in human monocytes without modifying toll-like receptor 4 membrane expression.

Abstract：

:Toll-like receptor 4 (TLR4) participates in innate immunity by detecting lipopolysaccharides (LPS) of Gram-negative bacterial cell walls. TLR4 macrophage expression in mice is modulated by LPS. This fact constitutes, at least partially, the molecular basis for LPS tolerance. Very recently, the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, has been described on TLR4 membrane expression of human monocytes. IFN-gamma up-regulates TLR4 expression and antagonizes the LPS-induced TLR4 down-regulation. These data prompted us to study the expression of membrane TLR4 in human mono- cytes in which LPS tolerance was induced by LPS and by anti-inflammatory cytokines [interleukin-10 (IL-10) and transforming growth factor beta1 (TGFbeta1)]. Data concerning this latter model, and more specifically, the effect of anti-inflammatory cytokines over TLR4 expression, are not available at present. We show here that membrane TLR4 expression in human monocytes falls after LPS exposure. The effect was prolonged for 12 h, but then expression returned to normal levels. The incubation of human monocytes with IL-10, TGFbeta1 or a mixture of both induces no alterations in membrane TLR4 expression. However, these cytokines are able to substitute the tolerizing LPS exposure in order to induce LPS tolerance. Our data help to achieve a better understanding of the way cytokines control the cellular expression of TLR.

journal_name

Scand J Immunol

journal_title

Scandinavian journal of immunology

authors

Moreno C,Merino J,Vázquez B,Ramírez N,Echeverría A,Pastor F,Sánchez-Ibarrola A

doi

10.1111/j.0300-9475.2004.01445.x

keywords:

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

553-8

issue

6

eissn

0300-9475

issn

1365-3083

pii

SJI1445

journal_volume

59

pub_type

杂志文章

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