EurekaMag.com logo
+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages



Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages



Journal of Immunology 169(5): 2354-2360



CD40 is a type I membrane-bound molecule belonging to the TNFR superfamily that is expressed on various immune cells including macrophages and microglia. The aberrant expression of CD40 is involved in the initiation and maintenance of various human diseases including multiple sclerosis, arthritis, atherosclerosis, and Alzheimer's disease. Inhibition of CD40 signaling has been shown to provide a significant beneficial effect in a number of animal models of human diseases including the aforementioned examples. We have previously shown that IFN-gamma induces CD40 expression in macrophages and microglia. IFN-gamma leads to STAT-1alpha activation directly and up-regulation of NF-kappaB activity due to the secretion and subsequent autocrine signaling of TNF-alpha. However, TNF-alpha alone is not capable of inducing CD40 expression in these cells. Suppressor of cytokine signaling 1 protein (SOCS-1) is a cytokine-inducible Src homology 2-containing protein that regulates cytokine receptor signaling by inhibiting STAT-1alpha activation via a specific interaction with activated Janus kinase 2. Given the important role of CD40 in inflammatory events in the CNS as well as other organ systems, it is imperative to understand the molecular mechanisms contributing to both CD40 induction and repression. We show that ectopic expression of SOCS-1 abrogates IFN-gamma-induced CD40 protein expression, mRNA levels, and promoter activity. Additionally, IFN-gamma-induced TNF-alpha secretion, as well as STAT-1alpha and NF-kappaB activation, are inhibited in the presence of SOCS-1. We conclude that SOCS-1 inhibits cytokine-induced CD40 expression by blocking IFN-gamma-mediated STAT-1alpha activation, which also then results in suppression of IFN-gamma-induced TNF-alpha secretion and subsequent NF-kappaB activation.

(PDF emailed within 0-6 h: $19.90)

Accession: 011428712

Download citation: RISBibTeXText

PMID: 12193701

DOI: 10.4049/jimmunol.169.5.2354



Related references

Suppressor of cytokine signaling -1 inhibits cytokine induction of CD40 expression in murine macrophages. FASEB Journal 16(4): A319, March 20, 2002

IL-10 inhibits lipopolysaccharide-induced CD40 gene expression through induction of suppressor of cytokine signaling-3. Journal of Immunology 177(11): 7761-7771, 2006

Suppressor of cytokine signaling 3 inhibits head kidney macrophage activation and cytokine expression in Scophthalmus maximus. Developmental and Comparative Immunology 35(2): 174-181, 2011

Stat5a inhibits IL-12-induced Th1 cell differentiation through the induction of suppressor of cytokine signaling 3 expression. Journal of Immunology 174(7): 4105-4112, 2005

Suppressor of cytokine signaling 1/JAB and suppressor of cytokine signaling 3/cytokine-inducible SH2 containing protein 3 negatively regulate the signal transducers and activators of transcription signaling pathway in normal human epidermal keratinocytes. Journal of Investigative Dermatology 120(4): 571-580, 2003

Expression of suppressor of cytokine signaling 3 (SOCS3) and cytokine-inducible Src homology 2-containing protein (CIS) induced in Burkholderia pseudomallei--infected mouse macrophages requires bacterial internalization. Microbial Pathogenesis 42(2-3): 104-110, 2007

Burkholderia pseudomallei-induced expression of suppressor of cytokine signaling 3 and cytokine-inducible src homology 2-containing protein in mouse macrophages: a possible mechanism for suppression of the response to gamma interferon stimulation. Infection and Immunity 73(11): 7332-7339, 2005

Suppressor of cytokine signaling 3 inhibits antiviral IFN-beta signaling to enhance HIV-1 replication in macrophages. Journal of Immunology 185(4): 2393-2404, 2010

Induction of Suppressor of Cytokine Signaling-1 by Toxoplasma gondii Contributes to Immune Evasion in Macrophages by Blocking IFN-g Signaling. Journal of Immunology 176(3): 40-7, 2006

Induction of suppressor of cytokine signaling-1 by Toxoplasma gondii contributes to immune evasion in macrophages by blocking IFN-gamma signaling. Journal of Immunology 176(3): 1840-1847, 2006

An impaired interferon-gamma signaling pathway in Leishmania-infected human macrophages is associated with the induction of suppressor of cytokine signaling-3. American Journal of Tropical Medicine & Hygiene 62(3 Supplement): 153, March, 2000

Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death. Cellular and Molecular Life Sciences 66(23): 3787-3795, 2009

Listeria monocytogenes modulates macrophage cytokine responses through STAT serine phosphorylation and the induction of suppressor of cytokine signaling 3. Journal of Immunology 166(1): 466-472, 2000

Listeria monocytogenes modulates macrophage cytokine responses through STAT serine phosphorylation and the induction of suppressor of cytokine signaling 3. Journal of Immunology 166(1): 6-72, 2001