Suppressor of cytokine signalling protein SOCS3 expression is increased at sites of acute and chronic inflammation

Abstract

Treatment of cells with cytokines and growth factors leads to the synthesis of Suppressor of Cytokine Signalling (SOCS) proteins that act as potent negative regulators of signalling via the Jak/STAT pathway. We used immunohistochemistry to identify cells and pathologies where SOCS3 expression might influence acute and chronic inflammatory responses in human tissues. Epitope and GFP tagged SOCS3 fusion proteins were localised predominantly in the nucleus of transfected cells and a validated anti SOCS3 antiserum revealed the expression of SOCS3 in the nucleus and cytoplasm of macrophages, endothelial and epithelial cells in a wide range of normal tissues in tissue microarrays (n = 31 different tissues). Nuclear SOCS3 was only seen in cells expressing a high level of the protein. Comparative immunostaining of acute, chronically and granulomatously inflamed human tissues revealed higher levels of nuclear and cytoplasmic SOCS3 expression in inflamed than in corresponding normal tissues, particularly in recruited leukocyte populations, but also in epithelia. The staining appeared more intense, suggesting higher expression levels, in areas where inflammation was more acute, consistent with the time course of SOCS3 induction described in vitro. Expression of SOCS3 protein by leucocytes and other cell types in tissue sections could be a useful marker of cells undergoing acute or chronic stimulation by cytokines in vivo.

The Spleen Promotes the Secretion of CCL2 and Supports an M1 Dominant Phenotype in Hepatic Macrophages During Liver Fibrosis

“…It has previously been reported that SOCS3 expression is increased during both acute and chronic inflammation [41]. Gordon et al reported that SOCS3 siRNA-mediated gene silencing in M1-activated human monocyte-derived macrophages decreased the expression of proinflammatory factors [42].…”

Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase-Dependent SOCS-3 Gene Induction Requires c-Jun, Signal Transducer and Activator of Transcription 3, and Specificity Protein 3 Transcription Factors

“…SOCS-3 expression is increased, however, at sites of acute and chronic inflammation (White et al, 2011), and IL-6 has been reported to promote acute and chronic inflammatory disease in the absence of SOCS-3 (Croker et al, 2012). Moreover, conditional deletion of the SOCS-3 gene in hematopoietic and endothelial cells of transgenic mice results in death caused by severe inflammatory lesions in the peritoneal and pleural cavities (Croker et al, 2008).…”

Gene delivery of suppressors of cytokine signaling (SOCS) inhibits inflammation and atherosclerosis development in mice

“…SOCS proteins regulate development, homeostasis and disease pathogenesis [34]. Indeed, SOCS expression is found increased in inflamed human tissues [37], making them potential markers of ongoing inflammation. Furthermore, loss-and gain-of-function studies evidenced the important role of SOCS proteins in regulating the course of inflammation in different experimental models [6,21,27,35], including cardiovascular diseases [32].…”