Review Article
Updating interleukin-6 classic- and trans-signaling
Jürgen Scheller, Joachim Grötzinger,
Stefan Rose-John,
Joachim Grötzinger
Department of Biochemistry, Christian-Albrechts-Universität, Kiel, Germany. Fax: +49 431 880 2007
Search for more papers by this authorStefan Rose-John
Department of Biochemistry, Christian-Albrechts-Universität, Kiel, Germany. Fax: +49 431 880 2007
Search for more papers by this authorJürgen Scheller, Joachim Grötzinger,
Stefan Rose-John,
Joachim Grötzinger
Department of Biochemistry, Christian-Albrechts-Universität, Kiel, Germany. Fax: +49 431 880 2007
Search for more papers by this authorStefan Rose-John
Department of Biochemistry, Christian-Albrechts-Universität, Kiel, Germany. Fax: +49 431 880 2007
Search for more papers by this authorAbstract
The cytokine interleukin-6 has been identified and cloned among others as B-cell stimulatory factor, hepatocyte stimulating factor, plasmacytoma growth factor, and interferon beta-2. Consequently, it emerged, that IL-6 controls a huge variety of cellular functions, among them induction of the acute phase response in the liver, mediation of inflammation and malignant transformation. In this review, we summarize the so called classical IL-6 signaling, which is mediated by the complex of IL-6, the membrane bound IL-6R and two gp130 molecules, and an alternative pathway called trans-signaling, which apparently contributes to the development of chronic inflammation and cancer. During trans-signaling an agonistic soluble IL-6R is generated, which sensitizes cells lacking the membrane bound IL-6R. Finally, we discuss specific inhibition of IL-6-trans-signaling processes by a naturally occurring soluble form of gp130, demonstrating that this protein may emerge as an important future therapeutic in clinical applications for chronic inflammation.
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