Therapeutic blockade of the interleukin-6 receptor (IL-6R) allows sIL-6R generation by proteolytic cleavage

被引：7
|
作者：
Prenissl, Niklas [1 ]
Lokau, Juliane [2 ]
Rose-John, Stefan [1 ]
Haybaeck, Johannes [2 ,3 ,4 ]
Garbers, Christoph [2 ]
机构：
[1] Univ Kiel, Inst Biochem, D-24118 Kiel, Germany
[2] Otto von Guericke Univ, Dept Pathol, Med Fac, Magdeburg, Germany
[3] Med Univ Graz, Inst Pathol, Graz, Austria
[4] Med Univ Innsbruck, Inst Pathol, Innsbruck, Austria
来源：
CYTOKINE | 2019年 / 114卷
关键词：
Interleukin-6; receptor; Trans-signaling; Proteolysis; Tocilizumab;
D O I：
10.1016/j.cyto.2018.11.023
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Blockade of the interleukin-6 receptor (IL-6R) is a successful therapeutic strategy in various inflammatory diseases. IL-6 can signal via membrane-bound (classic signaling) and soluble forms (sIL-6R, trans-signaling) of the IL-6R. Trans-signaling is causative for the pro-inflammatory properties of IL-6, and the selective inhibition of this pathway holds the promise to cause less side effects than the global blockade of IL-6 signaling. We have recently shown that the majority of sIL-6R in humans is generated by proteolytic cleavage of the membrane-bound IL-6R, but whether this process is influenced by therapeutic blockade of the IL-6R is unknown. In this study, we show that the monoclonal antibody tocilizumab and a single chain antibody directed against the IL-6R efficiently block IL-6 signaling, but do not prevent the proteolytic generation of sIL-6R.
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页码：1 / 5
页数：5
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