期刊
CYTOKINE
卷 144, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2021.155577
关键词
Cytokine; Cytokine receptor; Interleukin-6; GP130; Trans-signaling; Soluble receptor; blood-buffer
资金
- Deutsche Forschungsgemeinschaft, Bonn, Germany [CRC841, CRC877]
- Cluster of Excellence 306 Inflammation at Interfaces
- German Cancer Aid
IL-6 is a cytokine involved in immunity, neural cell maintenance, and metabolism. It is synthesized by various cells and its levels are elevated during infection and inflammation. IL-6 binds to a receptor complex and can also act on cells without the IL-6 receptor through trans-signaling.
Interleukin-6 (IL-6) is a cytokine, which is involved in innate and acquired immunity, in neural cell maintenance and in metabolism. IL-6 can be synthesized by many different cells including myeloid cells, fibroblasts, endothelial cells and lymphocytes. The synthesis of IL-6 is strongly stimulated by Toll like receptors and by IL-1. Therefore, IL-6 levels in the body are high during infection and inflammatory processes. Moreover, IL-6 is a prominent growth factor of tumor cells and plays a major role in inflammation associated cancer. On target cells, IL-6 binds to an IL-6 receptor, which is not signaling competent. The complex of IL-6 and IL-6 receptor associate with a second receptor subunit, glycoprotein gp130, which dimerizes and initiates intracellular signaling. Cells, which do not express the IL-6 receptor are not responsive to IL-6. They can, however, be stimulated by the complex of IL-6 and a soluble form of the IL-6 receptor, which is generated by limited proteolysis and to a lesser extent by translation from an alternatively spliced mRNA. This process has been named IL-6 trans-signaling. This review article will explain the biology of IL-6 trans-signaling and the specific inhibition of this mode of signaling, which has been recognized to be fundamental in inflammation and cancer.
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