Nitric oxide induces SOCS-1 expression in human monocytes in a TNF-α-dependent manner

In contrast to the thoroughly characterized mechanisms of positive regulation within cytokine signaling pathways, our knowledge of negative feedback loops is comparatively sparse. We and others have previously reported that IRAK-M down-regulates inflammatory responses to multiple stimuli. In particu...

Full description

Saved in:
Bibliographic Details
Published in:Journal of endotoxin research 2006-10, Vol.12 (5), p.296-306
Main Authors: González-León, M. Carmen, Soares-Schanoski, Alessandra, del Fresno, Carlos, Cimadevila, Agata, Goméz-Piña, Vanesa, Mendoza-Barberá, Elena, García, Felipe, Marín, Elvira, Arnalich, Francisco, Fuentes-Prior, Pablo, López-Collazo, Eduardo
Format: Article
Language:English
Subjects:
Cells, Cultured
Humans
Kinetics
Monocytes - drug effects
Monocytes - metabolism
Nitric Oxide - pharmacology
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins - genetics
Suppressor of Cytokine Signaling Proteins - metabolism
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In contrast to the thoroughly characterized mechanisms of positive regulation within cytokine signaling pathways, our knowledge of negative feedback loops is comparatively sparse. We and others have previously reported that IRAK-M down-regulates inflammatory responses to multiple stimuli. In particular, we could show that the nitric oxide (NO) donor, GSNO, induces IRAK-M overexpression in human monocytes. Here we study the expression of another important negative regulator of cytokine signaling, SOCS-1, in human monocytes exposed to GSNO. The NO donor induced significant levels of SOCS-1 mRNA and protein, 6 h and 16 h after stimulation, respectively. Monocytes stimulated with GSNO for longer periods (24 h and 48 h) failed to express IL-6 and IP-10 upon LPS challenge. In addition, and in line with previous reports of NO-mediated induction of TNF-α, we have found that exposure to this cytokine induces SOCS-1 mRNA in human monocytes. A blocking antibody against TNF-α impaired SOCS-1 expression upon GSNO treatment and re-instated IL-6 and IP-10 mRNA levels after LPS challenge in cultures pretreated with the NO donor. We conclude that NO stimulates SOCS-1 overexpression in a pathway at least partially regulated by TNF-α.
ISSN:0968-0519
DOI:10.1177/09680519060120050501