In:
Journal of Endotoxin Research, SAGE Publications, Vol. 12, No. 5 ( 2006-10), p. 296-306
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0968-0519
DOI:
10.1177/09680519060120050501
Language:
English
Publisher:
SAGE Publications
Publication Date:
2006
detail.hit.zdb_id:
2381250-3
