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Respiratory Research
Published in: Respiratory Research 1/2007

Open Access 01-12-2007 | Research

LPS induces IL-10 production by human alveolar macrophages via MAPKinases- and Sp1-dependent mechanisms

Authors: Hugues Chanteux, Amélie C Guisset, Charles Pilette, Yves Sibille

Published in: Respiratory Research | Issue 1/2007

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Abstract

Background

IL-10 is a cytokine mainly produced by macrophages that plays key roles in tolerance to inhaled antigens and in lung homeostasis. Its regulation in alveolar macrophages (HAM), the resident lung phagocytes, remains however unknown.

Methods

The present study investigated the role of intracellular signalling and transcription factors controlling the production of IL-10 in LPS-activated HAM from normal nonsmoking volunteers.

Results

LPS (1–1000 pg/ml) induced in vitro IL-10 production by HAM, both at mRNA and protein levels. LPS also activated the phosphorylation of ERK, p38 and JNK MAPkinases (immunoblots) and Sp-1 nuclear activity (EMSA). Selective inhibitors of MAPKinases (respectively PD98059, SB203580 and SP600125) and of Sp-1 signaling (mithramycin) decreased IL-10 expression in HAM. In addition, whilst not affecting IL-10 mRNA degradation, the three MAPKinase inhibitors completely abolished Sp-1 activation by LPS in HAM.

Conclusion

These results demonstrate for the first time that expression of IL-10 in lung macrophages stimulated by LPS depends on the concomitant activation of ERK, p38 and JNK MAPKinases, which control downstream signalling to Sp-1 transcription factor. This study further points to Sp-1 as a key signalling pathway for IL-10 expression in the lung.
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Metadata
Title
LPS induces IL-10 production by human alveolar macrophages via MAPKinases- and Sp1-dependent mechanisms
Authors
Hugues Chanteux
Amélie C Guisset
Charles Pilette
Yves Sibille
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2007
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-8-71

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