IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6

International Journal of Biological Sciences
Stefan Rose-John

Abstract

Interleukin-6 (IL-6) is a cytokine with many activities. It has functions in the regulation of the immune system and the nervous system. Furthermore, IL-6 is involved in liver regeneration and in the metabolic control of the body. On target cells, IL-6 binds to an 80 kDa IL-6 receptor (IL-6R). The complex of IL-6 and IL-6R associates with a second protein, gp130, which thereupon dimerizes and initiates intracellular signaling. Whereas gp130 is expressed on all cells, IL-6R is only present on few cells in the body including hepatocytes and some leukocytes. Cells, which do not express IL-6R cannot respond to the cytokine, since gp130 alone has no measurable affinity for IL-6. Interestingly, a soluble form of IL-6R (sIL-6R) comprising the extracellular portion of the receptor can bind IL-6 with a similar affinity as the membrane bound IL-6R. The complex of IL-6 and sIL-6R can bind to gp130 on cells, which do not express the IL-6R, and which are unresponsive to IL-6. This process has been called trans-signaling. Here I will review published evidence that IL-6 trans-signaling is pro-inflammatory whereas classic IL-6 signaling via the membrane bound IL-6R is needed for regenerative or anti-inflammatory activities of the cytokine. Fur...Continue Reading

References

Dec 15, 1992·Biochemical and Biophysical Research Communications·J MüllbergS Rose-John
May 31, 1990·European Journal of Biochemistry·S Rose-JohnP C Heinrich
Oct 1, 1990·Immunology Today·J F Bazan
Oct 1, 1989·The Journal of Experimental Medicine·D NovickM Rubinstein
May 1, 1994·International Journal of Cancer. Journal International Du Cancer·G ScambiaS Mancuso
Oct 11, 1993·FEBS Letters·J MüllbergS Rose-John
Feb 1, 1993·European Journal of Immunology·J MüllbergS Rose-John
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·I WalevS Rose-John
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·P MärzS Rose-John
Feb 2, 1999·The Journal of Experimental Medicine·S A JonesG M Fuller
Jun 10, 2000·European Journal of Biochemistry·S H HoischenS Rose-John
Dec 20, 2000·European Journal of Biochemistry·T JostockS Rose-John
Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·J AudetC J Eaves
Mar 14, 2003·FEBS Letters·Björn SchusterKarl-Josef Kallen
May 30, 2003·The Biochemical Journal·Peter C HeinrichFred Schaper
Jul 2, 2003·The Journal of Biological Chemistry·Vance MatthewsStefan Rose-John
Jul 28, 2004·Stem Cells·Rohan K HumphreyAlberto Hayek
Dec 21, 2004·Biochemical and Biophysical Research Communications·Jürgen SchellerStefan Rose-John
Jan 26, 2005·The Journal of Clinical Investigation·Aysefa DoganciSusetta Finotto
Mar 18, 2005·Annual Review of Immunology·Tadamitsu Kishimoto
Oct 29, 2005·Journal of Cell Science·Bernd GieseGerhard Müller-Newen
Jan 10, 2006·Annals of the New York Academy of Sciences·L VitettaA Sali
May 19, 2006·Journal of Leukocyte Biology·Stefan Rose-JohnSimon A Jones
Jun 16, 2006·Biochemical and Biophysical Research Communications·Stephanie TenhumbergStefan Rose-John

❮ Previous
Next ❯

Citations

May 30, 2013·Breast Cancer Research and Treatment·Julia HobsonMercedes Rincon
Nov 16, 2013·The Journal of Clinical Investigation·Maya KansaraDavid M Thomas
Mar 16, 2013·International Journal of Biological Sciences·Gustavo CarboneMercedes Rincon
Nov 9, 2012·International Journal of Biological Sciences·Mercedes Rincon
Dec 18, 2013·Current Rheumatology Reports·Stefanie Steiger, Jacquie L Harper
Feb 14, 2014·BioMed Research International·Yuji Yoshida, Toshio Tanaka
Mar 13, 2014·Der Internist·S Schreiber, O Bachmann
Dec 12, 2013·Seminars in Immunology·Jürgen SchellerStefan Rose-John
Mar 7, 2014·Seminars in Immunology·Toshio TanakaTadamitsu Kishimoto
Feb 21, 2014·Seminars in Immunology·Koji Taniguchi, Michael Karin
Mar 8, 2014·Seminars in Immunology·Daniel T FisherSharon S Evans
May 24, 2014·Nature Reviews. Drug Discovery·Marc Y Donath
Aug 16, 2014·Journal of Immunology Research·Andrea SagginiAndrea Chiricozzi
Aug 20, 2014·Nature Reviews. Rheumatology·Leonard H Calabrese, Stefan Rose-John
Feb 27, 2015·Biochemistry. Biokhimii︠a︡·I V AstrakhantsevaS A Nedospasov
Dec 25, 2013·Arthritis Research & Therapy·David S Pisetsky
Mar 20, 2014·The Journal of Clinical Investigation·Matjaz RokavecHeiko Hermeking
Feb 18, 2016·Clinica Chimica Acta; International Journal of Clinical Chemistry·Somaiya MateenSwaleha Zubair
Feb 16, 2016·Cell Reports·Juliane LokauChristoph Garbers
Jan 15, 2015·Expert Opinion on Investigational Drugs·Trehani M FonsekaSidney H Kennedy
Apr 29, 2014·Expert Opinion on Investigational Drugs·Luca SemeranoMarie-Christophe Boissier
May 11, 2013·Climacteric : the Journal of the International Menopause Society·M BorgJ Calleja-Agius
Feb 13, 2016·Journal of Hepatology·Dirk Schmidt-Arras, Stefan Rose-John
Jan 24, 2016·Biochimica Et Biophysica Acta·Susanne Sattler, Nadia Rosenthal
Mar 19, 2014·Metabolism: Clinical and Experimental·Anna WonnerthThomas W Weiss
Nov 26, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Ingo Kleiter, Ralf Gold
Apr 16, 2013·Biochemical and Biophysical Research Communications·Xiao LiuJiong Li
Sep 1, 2014·Developmental and Comparative Immunology·Jipseol JeongWongi Min
Dec 3, 2015·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Priscila C LimaEliane C Arantes
Nov 3, 2015·Best Practice & Research. Clinical Endocrinology & Metabolism·Stefan Rose-John
Jul 7, 2015·Brain, Behavior, and Immunity·Carlos N OyanedelStefan Rose-John
Apr 5, 2014·British Journal of Pharmacology·Dan QuYu Huang

❮ Previous
Next ❯

Methods Mentioned

BETA
PMA
transgenic

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.