SOCS3 in immune regulation of inflammatory bowel disease and inflammatory bowel disease-related cancer

Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
Cytokine & growth factor reviews (Impact Factor: 5.36). 05/2012; 23(3):127-38. DOI: 10.1016/j.cytogfr.2012.04.005
Source: PubMed


Inflammatory bowel disease (IBD) has unclear pathogenesis and it is related to the increasing risk of developing colorectal cancer (CRC). Recent studies have uncovered the molecular mechanism of intracellular signaling pathways of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-6. The major transcription factors including STAT3 have been shown to play a major role in transmitting inflammatory cytokine signals to the nucleus. The suppressors of cytokine signaling (SOCS) 3 protein is the key physiological regulators of cytokine-mediated STAT3 signaling. As such it influences the development of inflammatory and malignant disorders like this associated with IBD. Here we review the complex function of SOCS3 in innate and adaptive immunity, different cell types (macrophages, neutrophils, dendritic cells, B cells, T cells and intestinal epithelial cells) and the role of SOCS3 on the pathogenesis of inflammatory bowel disease (IBD) and IBD-related cancer. Finally, we explore how this knowledge may open novel avenues for the rational treatment of IBD and IBD-related cancer.

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    • "SOCS3 inhibits the production of IL-2, a cytokine crucial for the activation of T cells, effectively inhibiting initial T cell activation. The over-expression of SOCS3 in this setting might therefore be the result of an effort to limit the activation of T helper cells in the inflamed mucosa, while the increased expression of STAT3 might be the result of SOCS3-independent activation via IL10[51], [52]. It is also possible that the SOCS3 expression detected stems from cells other than the lymphocytes, as both neutrophils, macrophages and epithelial cells have been shown to express SOCS3 in IBD mucosa[53]. "
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    • "The dietary feeding of crocin significantly suppressed several inflammatory events and NF-κB expression in the colorectal mucosa of the mice that received DSS. Inflammatory genes, such as COX2, iNOS, TNF-α, and IL-1β, are the most common target genes participating in the activation of NF-κB and are associated with a number of chronic inflammatory diseases, including IBD and IBD-related colorectal carcinogenesis [37, 38, 45, 46, 62]. In the current study, we observed decreases in the mRNA expression levels of NF-κB, COX-2, iNOS, TNF-α, IL-1β, and IL-6 in the mice treated with DSS and crocin when compared to the mice given DSS alone. "
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