Coordination of interleukin-6 biology by membrane bound and soluble receptors

2001 ◽  
pp. 145-151 ◽  
Author(s):  
Stefan Rose-John
Keyword(s):  
Interleukin 6 ◽  
Soluble Receptors ◽  
Membrane Bound

scholarly journals Inducible microRNA-590-5p inhibits host antiviral response by targeting the soluble interleukin-6 (IL6) receptor

2018 ◽  
Vol 293 (47) ◽  
pp. 18168-18179 ◽  
Author(s):  
Yaqin Zhou ◽  
Zhangchuan Xia ◽  
Zhikui Cheng ◽  
Gang Xu ◽  
Xiaodan Yang ◽  
...  
Keyword(s):  
Viral Infection ◽  
Interleukin 6 ◽  
Underlying Mechanism ◽  
Antiviral Response ◽  
Type I ◽  
Interleukin 6 Receptor ◽  
Important Regulator ◽  
Membrane Bound ◽  
Host Antiviral Response

MicroRNA (miR)-590-5p has been identified as an important regulator of some signaling pathways such as cell proliferation and tumorigenesis. However, little is known about its role during viral infection. Here, we report that miR-590-5p was significantly induced by various viruses and effectively potentiated virus replication in different viral infection systems. Furthermore, miR-590-5p substantially attenuated the virus-induced expression of type I and type III interferons (IFNs) and inflammatory cytokines, resulting in impaired downstream antiviral signaling. Interleukin-6 receptor (IL6R) was identified as a target of miR-590-5p. Interestingly, the role of miR-590-5p in virus-triggered signaling was abolished in IL6R knockout cells, and this could be rescued by restoring the expression of the soluble IL6R (sIL6R) but not the membrane-bound IL6R (mIL6R), suggesting that sIL6R is indispensable for miR-590-5p in modulating the host antiviral response. Furthermore, miR-590-5p down-regulated endogenous sIL6R and mIL6R expression through a translational repression mechanism. These findings thus uncover a previously uncharacterized role and the underlying mechanism of miR-590-5p in the innate immune response to viral infection.

The response of plasma interleukin-6 and its soluble receptors to exercise in the cold in humans

2008 ◽  
Vol 26 (9) ◽  
pp. 927-933 ◽  
Author(s):  
Stephen Patterson ◽  
Suzanne Reid ◽  
Stuart Gray ◽  
Myra Nimmo
Keyword(s):  
Interleukin 6 ◽  
Soluble Receptors

The role of interleukin-6 and of its soluble receptors in the biocompatibility of dialysis treatment

2004 ◽  
Vol 24 (5) ◽  
pp. 492-494 ◽  
Author(s):  
Bruno Memoli ◽  
Giuseppina Romano ◽  
Rosamunda D’Arcangelo ◽  
Marco Del Prete ◽  
Pasquale Esposito ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Soluble Receptors ◽  
Dialysis Treatment

scholarly journals SorLA in Interleukin-6 Signaling and Turnover

2017 ◽  
Vol 37 (11) ◽  
Author(s):  
Jakob Vejby Larsen ◽  
Claus Munck Petersen
Keyword(s):  
Complex Formation ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Carrier Protein ◽  
Enzymatic Cleavage ◽  
Present Evidence ◽  
Signaling Complex ◽  
Pathological Conditions ◽  
Membrane Bound ◽  
Multifunctional Cytokine

ABSTRACT Interleukin-6 (IL-6) is a multifunctional cytokine with important functions in various physiologic processes. Mice lacking IL-6 exhibit multiple phenotypic abnormalities, such as an inadequate immune and acute-phase response, and elevated levels of circulating IL-6 have been found to accompany several pathological conditions. IL-6 binds the nonsignaling IL-6 receptor (IL-6R), which is expressed as a transmembrane, as well as a secreted circulating protein, before it engages homodimeric gp130 for signaling. Complex formation between IL-6 and the membrane-bound IL-6 receptor gives rise to classic cis signaling, whereas complex formation between IL-6 and the soluble IL-6R results in trans signaling. Here, we report that the endocytic receptor SorLA targets IL-6 and IL-6R. We present evidence that SorLA mediates efficient cellular uptake of both IL-6 and the circulating IL-6R in astrocytes. We further show that SorLA interacts with the membrane-bound IL-6R at the cell surface and thereby downregulates IL-6 cis signaling. Finally, we find that the SorLA ectodomain, released from the cell membrane upon enzymatic cleavage of full-length SorLA, may act as an IL-6 carrier protein that stabilizes IL-6 and its capacity for trans signaling.

Serum Levels of Interleukin-6 and Its Soluble Receptors in Patients with Hepatitis C Virus Infection

2006 ◽  
Vol 67 (1-2) ◽  
pp. 27-32 ◽  
Author(s):  
Kiyoshi Migita ◽  
Seigo Abiru ◽  
Yumi Maeda ◽  
Manabu Daikoku ◽  
Kazuyuki Ohata ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Interleukin 6 ◽  
Serum Levels ◽  
Hepatitis C Virus Infection ◽  
Soluble Receptors

scholarly journals Transgenic inhibition of interleukin-6 trans-signaling does not prevent skeletal pathologies in mucolipidosis type II mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Marie Westermann ◽  
Anke Baranowsky ◽  
Giorgia Di Lorenzo ◽  
Tatyana Danyukova ◽  
Jamie Soul ◽  
...  
Keyword(s):  
Bone Mass ◽  
Interleukin 6 ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Elevated Expression ◽  
Pharmacological Blockade ◽  
Natural Inhibitor ◽  
Membrane Bound ◽  
Soluble Fusion Protein ◽  
Mucolipidosis Type

AbstractSevere skeletal alterations are common symptoms in patients with mucolipidosis type II (MLII), a rare lysosomal storage disorder of childhood. We have previously reported that progressive bone loss in a mouse model for MLII is caused by an increased number of bone-resorbing osteoclasts, which is accompanied by elevated expression of the cytokine interleukin-6 (IL-6) in the bone microenvironment. In the present study we addressed the question, if pharmacological blockade of IL-6 can prevent the low bone mass phenotype of MLII mice. Since the cellular IL-6 response can be mediated by either the membrane-bound (classic signaling) or the soluble IL-6 receptor (trans-signaling), we first performed cell culture assays and found that both pathways can increase osteoclastogenesis. We then crossed MLII mice with transgenic mice expressing the recombinant soluble fusion protein sgp130Fc, which represents a natural inhibitor of IL-6 trans-signaling. By undecalcified histology and bone-specific histomorphometry we found that high circulating sgp130Fc levels do not affect skeletal growth or remodeling in wild-type mice. Most importantly, blockade of IL-6 trans-signaling did neither reduce osteoclastogenesis, nor increase bone mass in MLII mice. Therefore, our data clearly demonstrate that the bone phenotype of MLII mice cannot be corrected by blocking the IL-6 trans-signaling.

scholarly journals Interleukin-6 receptor genetic variation and tocilizumab treatment response to COVID-19

2021 ◽  
Author(s):  
Ammar Ali Almarzooq
Keyword(s):  
Genetic Variation ◽  
Interleukin 6 ◽  
Treatment Efficacy ◽  
European Ancestry ◽  
Asian Populations ◽  
Inflammatory Conditions ◽  
African Populations ◽  
Interleukin 6 Receptor ◽  
Membrane Bound ◽  
Sub Saharan

ABSTRACTInterleukin-6 receptor (IL6R) stimulates the inflammatory pathways as part of the acute-phase response to infection. Tocilizumab is a monoclonal antibody that inhibits both membrane-bound and soluble IL6R and is used to treat inflammatory conditions, including COVID-19. Despite the disproportionate incidence of COVID-19 among underserved, racial, and ethnic minority populations, the efficacy of tocilizumab in hospitalized COVID-19 patients from these populations is unclear. In this work, three genetic markers for the IL6R gene were analyzed across diverse ethnic backgrounds to identify population differences in response to tocilizumab treatment. Genetic structure analyses showed that African populations were significantly different from other described populations. In addition, mapped frequencies of these alleles showed that Sub-Saharan African populations were 3.4x more likely to show an impaired response to tocilizumab than East Asian populations, and 1.8x more likely than European ancestry populations. Existing IL6R genotype results may identify populations at increased therapeutic failure risk. As results from current clinical trials on the efficacy of tocilizumab treatment for extreme COVID-19 infections are conflicting, more studies are needed across diverse patient backgrounds to better understand the genetic factors necessary to predict treatment efficacy. This work demonstrates how pharmacogenomics studies can elucidate genetic variation on treatment efficacy on COVID-19.

Comparison of plant hormone signalling systems

2015 ◽  
Vol 58 ◽  
pp. 165-181 ◽  
Author(s):  
Antoine Larrieu ◽  
Teva Vernoux
Keyword(s):  
Small Molecules ◽  
Plant Hormone ◽  
Model Systems ◽  
Regulatory Proteins ◽  
Plant Growth And Development ◽  
Soluble Receptors ◽  
Membrane Bound ◽  
Similarities And Differences ◽  
Signalling Systems ◽  
Hormone Signalling

Plant growth and development are controlled by nine structurally distinct small molecules termed phytohormones. Over the last 20 years, the molecular basis of their signal transduction, from receptors to transcription factors, has been dissected using mainly Arabidopsis thaliana and rice as model systems. Phytohormones can be broadly classified into two distinct groups on the basis of whether the subcellular localization of their receptors is in the cytoplasm or nucleus, and hence soluble, or membrane-bound, and hence insoluble. Soluble receptors, which control the responses to auxin, jasmonates, gibberellins, strigolactones and salicylic acid, signal either directly or indirectly via the destruction of regulatory proteins. Responses to abscisic acid are primarily mediated by soluble receptors that indirectly regulate the phosphorylation of targeted proteins. Insoluble receptors, which control the responses to cytokinins, brassinosteroids and ethylene, transduce their signal through protein phosphorylation. This chapter provides a comparison of the different components of these signalling systems, and discusses the similarities and differences between them.

Membrane-bound and Soluble Interleukin-6 Receptor: Studies on Structure, Regulation of Expression, and Signal Transductiona

2006 ◽  
Vol 762 (1) ◽  
pp. 222-237 ◽  
Author(s):  
PETER C. HEINRICH ◽  
LUTZ GRAEVE ◽  
STEFAN ROSE-JOHN ◽  
JENS SCHNEIDER-MERGENER ◽  
ELKE DITTRICH ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Regulation Of Expression ◽  
Interleukin 6 Receptor ◽  
Membrane Bound ◽  
Structure Regulation
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