The successful treatment of certain autoimmune conditions with the humanized anti–IL-6 receptor (IL-6R) antibody tocilizumab has emphasized the clinical importance of cytokines that signal through the β-receptor subunit glycoprotein 130 (gp130). In this Review, we explore how gp130 signaling controls disease progression and examine why IL-6 has a special role among these cytokines as an inflammatory regulator. Attention will be given to the role of the soluble IL-6R, and we will provide a perspective into the clinical blockade of IL-6 activity in autoimmunity, inflammation, and cancer.
Simon A. Jones, Jürgen Scheller, Stefan Rose-John
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Blockade of IL-6 Trans Signaling Attenuates Pulmonary Fibrosis
TT Le, H Karmouty-Quintana, E Melicoff, TT Le, T Weng, NY Chen, M Pedroza, Y Zhou, J Davies, K Philip, J Molina, F Luo, AT George, LJ Garcia-Morales, RR Bunge, BA Bruckner, M Loebe, H Seethamraju, SK Agarwal, MR Blackburn |
Journal of immunology (Baltimore, Md. : 1950) | 2014 |
Alternative Intronic Polyadenylation Generates the Interleukin-6 Trans-signaling Inhibitor sgp130-E10
J Sommer, C Garbers, J Wolf, A Trad, JM Moll, M Sack, R Fischer, J Grotzinger, GH Waetzig, DM Floss, J Scheller |
The Journal of biological chemistry | 2014 |
Role of Ubiquitylation in Controlling Suppressor of Cytokine Signalling 3 (SOCS3) Function and Expression
J Williams, K Munro, T Palmer |
Cells | 2014 |
Interleukin-6 signaling drives fibrosis in unresolved inflammation
CA Fielding, GW Jones, RM McLoughlin, L McLeod, VJ Hammond, J Uceda, AS Williams, M Lambie, TL Foster, CT Liao, CM Rice, CJ Greenhill, CS Colmont, E Hams, B Coles, A Kift-Morgan, Z Newton, KJ Craig, JD Williams, GT Williams, SJ Davies, IR Humphreys, VB O'Donnell, PR Taylor, BJ Jenkins, N Topley, SA Jones |
Immunity | 2014 |
IL-6 as a Druggable Target in Psoriasis: Focus on Pustular Variants
A Saggini, S Chimenti, A Chiricozzi |
Journal of Immunology Research | 2014 |
Interleukins in chronic liver disease: lessons learned from experimental mouse models
L Hammerich, F Tacke |
Clinical and experimental gastroenterology | 2014 |
The different shades of fat
V Peirce, S Carobbio, A Vidal-Puig |
Nature | 2014 |
Revisiting STAT3 signalling in cancer: new and unexpected biological functions
H Yu, H Lee, A Herrmann, R Buettner, R Jove |
Nature Reviews Cancer | 2014 |
Macrophage Polarization in Pancreatic Carcinoma: Role of Heparanase Enzyme
E Hermano, A Meirovitz, K Meir, G Nussbaum, L Appelbaum, T Peretz, M Elkin |
JNCI Journal of the National Cancer Institute | 2014 |
Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma
W Zhang, N Nandakumar, Y Shi, M Manzano, A Smith, G Graham, S Gupta, EE Vietsch, SZ Laughlin, M Wadhwa, M Chetram, M Joshi, F Wang, B Kallakury, J Toretsky, A Wellstein, C Yi |
Science signaling | 2014 |
Ectopic lymphoid-like structures in infection, cancer and autoimmunity
C Pitzalis, GW Jones, M Bombardieri, SA Jones |
Nature Reviews Immunology | 2014 |
Therapeutic effect of farnesylthiosalicylic acid on adjuvant-induced arthritis through suppressed release of inflammatory cytokines: FTS and arthritis
E Aizman, E Blacher, O Ben-Moshe, T Kogan, Y Kloog, A Mor |
Clinical & Experimental Immunology | 2014 |
Interleukin-6 Signaling, Soluble Glycoprotein 130, and Inflammation in Heart Failure
ET Askevold, L Gullestad, CP Dahl, A Yndestad, T Ueland, P Aukrust |
Current Heart Failure Reports | 2014 |
PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation
S Kolodziej, ON Kuvardina, T Oellerich, J Herglotz, I Backert, N Kohrs, E Buscató, SK Wittmann, G Salinas-Riester, H Bonig, M Karas, H Serve, E Proschak, J Lausen |
Nature Communications | 2014 |
Chemically modified DNA aptamers bind interleukin-6 with high affinity and inhibit signaling by blocking its interaction with interleukin-6 receptor
S Gupta, M Hirota, SM Waugh, I Murakami, T Suzuki, M Muraguchi, M Shibamori, Y Ishikawa, TC Jarvis, JD Carter, C Zhang, B Gawande, M Vrkljan, N Janjic, DJ Schneider |
The Journal of biological chemistry | 2014 |
IL-6 biology: implications for clinical targeting in rheumatic disease
LH Calabrese, S Rose-John |
Nature Reviews Rheumatology | 2014 |
Suppression of mucin 2 promotes interleukin-6 secretion and tumor growth in an orthotopic immune-competent colon cancer animal model
YS Shan, HP Hsu, MD Lai, MC Yen, JH Fang, TY Weng, YL Chen |
Oncology reports | 2014 |
Toll-like Receptor-Mediated Responses by Placental Hofbauer Cells (HBCs): A Potential Pro-Inflammatory Role for Fetal M2 Macrophages
OM Young, Z Tang, T Niven-Fairchild, S Tadesse, G Krikun, ER Norwitz, G Mor, VM Abrahams, S Guller |
American Journal of Reproductive Immunology | 2014 |
Discovery and characterization of olokizumab: A humanized antibody targeting interleukin-6 and neutralizing gp130-signaling
S Shaw, T Bourne, C Meier, B Carrington, R Gelinas, A Henry, A Popplewell, R Adams, T Baker, S Rapecki, D Marshall, A Moore, H Neale, A Lawson |
mAbs | 2014 |
Peripheral Nerve Regeneration and NGF-Dependent Neurite Outgrowth of Adult Sensory Neurons Converge on STAT3 Phosphorylation Downstream of Neuropoietic Cytokine Receptor gp130
S Quarta, BE Baeumer, N Scherbakov, M Andratsch, S Rose-John, G Dechant, CE Bandtlow, M Kress |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2014 |
A Disintegrin and Metalloprotease 17 Dynamic Interaction Sequence, the Sweet Tooth for the Human Interleukin 6 Receptor
S Düsterhöft, K Höbel, M Oldefest, J Lokau, GH Waetzig, A Chalaris, C Garbers, J Scheller, S Rose-John, I Lorenzen, J Grötzinger |
The Journal of biological chemistry | 2014 |
Pharmacologic Suppression of JAK1/2 by JAK1/2 Inhibitor AZD1480 Potently Inhibits IL-6-Induced Experimental Prostate Cancer Metastases Formation
L Gu, P Talati, P Vogiatzi, AL Romero-Weaver, J Abdulghani, Z Liao, B Leiby, DT Hoang, T Mirtti, K Alanen, M Zinda, D Huszar, MT Nevalainen |
Molecular cancer therapeutics | 2014 |
Control and consequences of IL-6 receptor ectodomain shedding
Scheller J |
European Journal of Medical Research | 2014 |
Clinical effects of soluble interleukin-6 receptor detection on autoimmune rheumatic disease patients
Chen M, Xu MH, Sun CX, Zhang Z, Du Y |
Pakistan Journal of Medical Sciences | 2014 |
Inhibition of protein kinase II (CK2) prevents induced signal transducer and activator of transcription (STAT) 1/3 and constitutive STAT3 activation
Aparicio-Siegmund S, Sommer J, Monhasery N, Schwanbeck R, Keil E, Finkenstädt D, Pfeffer K, Rose-John S, Scheller J, Garbers C |
Oncotarget | 2014 |