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

Published version
Peer-reviewed

Type

Article

Change log

Authors

White, Gemma E 
Cotterill, Andrew 
Addley, Mark R 
Soilleux, Elizabeth J 
Greaves, David R 

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.

Description

Keywords

Acute-Phase Reaction, Animals, Appendicitis, Biomarkers, CHO Cells, Cricetinae, Cricetulus, Female, Gene Expression, Genes, Reporter, Giant Cell Arteritis, HEK293 Cells, Humans, Inflammatory Bowel Diseases, Luciferases, Male, Organ Specificity, Protein Transport, Sarcoidosis, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins, Up-Regulation, beta-Galactosidase

Journal Title

J Mol Histol

Conference Name

Journal ISSN

1567-2379
1567-2387

Volume Title

42

Publisher

Springer Science and Business Media LLC