期刊
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
卷 29, 期 5, 页码 787-797出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.beem.2015.07.001
关键词
ADAM protease; cytokine; receptor; shedding; trans-signaling; inflammation; cancer
资金
- Deutsche Forschungs-gemeinschaft Bonn, Germany [SFB654, SFB841, 5FB877]
- Cluster of Excellence 'Inflammation at Interfaces'
Interleukin-6 is a cytokine involved in the regulation of the immune system and the central nervous system. Interleukin-6 binds to an interleukin-6 receptor, and then associates with a dimer of the ubiquitously expressed gp130 receptor subunit, which initiates intracellular signaling. The interleukin-6 receptor is found in a soluble form, which is generated by proteolytic cleavage and also to a minor extent by translation from an alternatively spliced mRNA. The complex of interleukin-6 bound to the interleukin-6 receptor can stimulate cells, which only express gp130. Such cells are not responsive to interleukin-6 alone. We have for the first time identified the molecular basis of pro-and anti-inflammatory properties of interleukin-6 and we have defined the generation of the soluble IL-6R as a crucial point in the regulation between these two properties. Furthermore, we have deduced a therapeutic principle, which enables us to exclusively block the pro-inflammatory activities of this important cytokine. (C) 2015 Published by Elsevier Ltd.
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