更新于：2024-11-01

IL-6RA x CNTFR

更新于：2024-11-01

基本信息

关联

项与 IL-6RA x CNTFR 相关的药物

KM-2702

靶点

CNTFR x IL-6RA

作用机制

CNTFR激动剂 [+1]

在研机构-

原研机构

Baker Heart & Diabetes Institute

在研适应症-

非在研适应症

2型糖尿病 [+2]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 IL-6RA x CNTFR 相关的临床结果

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100 项与 IL-6RA x CNTFR 相关的转化医学

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0 项与 IL-6RA x CNTFR 相关的专利（医药）

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项与 IL-6RA x CNTFR 相关的文献（医药）

2003-03-01·Journal of Biological Chemistry2区 · 生物学

Signaling of Human Ciliary Neurotrophic Factor (CNTF) Revisited

2区 · 生物学

Article

作者: Marina Kovaleva ; Stefan Rose-John ; Joachim Grötzinger ; Vance Matthews ; Karl-Josef Kallen ; Yi Sun ; Petra Regenhard ; Björn Schuster

Human ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that exerts a neuroprotective effect in multiple sclerosis and amyotrophic lateral sclerosis. Clinical application of human CNTF, however, was prevented by high toxicity at higher dosages. Human CNTF elicits cellular responses by induction of a receptor complex consisting of the CNTF alpha-receptor (CNTFR), which is not involved in signal transduction, and the beta-receptors gp130 and leukemia inhibitory factor receptor (LIFR). Previous studies with rat CNTF demonstrated that rat CNTF is unable to interact with the human interleukin-6 alpha-receptor, whereas at high concentrations, it can directly induce a signaling heterodimer of human gp130 and human LIFR in the absence of the CNTF receptor. Here, we demonstrate that human CNTF cannot directly induce a heterodimer of human gp130 and LIFR. However, human CNTF can use both the membrane-bound and the soluble human IL-6R as a substitute for its cognate alpha-receptor and thus widen the target spectrum of human CNTF. Engineering a CNTFR-specific human CNTF variant may therefore be a prerequisite to improving the safety profile of CNTF.

2001-01-01·Neurochemical Research3区 · 医学

Expression of mRNAs for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptors (CNTFR alpha, LIFR beta, IL-6R alpha, and gp130) in human peripheral neuropathies.

3区 · 医学

Article

作者: Gen Sobue ; Naoki Hattori ; Norimasa Mitsuma ; Mei Li ; Masahiko Yamamoto ; Yasuhiro Ito

The mRNA levels of neuropoietic cytokines, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and interleukin-6 (IL-6), and their receptor components (CNTFR alpha, LIFR beta, IL-6R alpha, and gp130) were examined in seventy-six patients with various peripheral neuropathies to determine the extent of expression of these cytokines and receptors, and their relationship to nerve fiber pathology and cell infiltration in the diseased nerves. The CNTF mRNA levels were significantly decreased in the diseased nerves and were correlated to residual myelinated fiber population. In contrast, the mRNA levels of LIF, IL-6 and the ligand-binding receptor components (CNTFR alpha, LIFR beta and IL-6R alpha) were elevated to variable extent in the diseased nerves. The CNTFR alpha, LIFR beta, and IL-6R alpha mRNA levels showed a weak positive correlation with the extent of demyelinating pathology and their levels were related to each other. Moreover, the CNTF and LIF mRNA levels were inversely proportional to the extent of macrophage invasion, whereas the CNTFR alpha and IL-6R alpha mRNA expressions were correlated to the increase in macrophage infiltration. The neuropoietic cytokine family and its receptor expressions in the diseased human nerves are regulated by an underlying pathology-related process rather than type of diseases, and could play a role in peripheral nerve regeneration and repair.

1999-02-15·Journal of Neuroscience Research3区 · 医学

Interleukin-6 (IL-6) and its soluble receptor support survival of sensory neurons

3区 · 医学

Article

作者: M. Thier ; J. Weis ; S. Rose-John ; P. März ; U. Otten

The cytokine interleukin-6 (IL-6) has multiple functions in the immune and hematopoietic systems. IL-6 is related to ciliary neurotrophic factor (CNTF), a trophic factor for motoneurons, sensory dorsal root ganglion (DRG) neurons, and other neuronal subpopulations. Both act via related receptor complexes, consisting of one ligand-specific alpha-receptor subunit (IL-6R and CNTFR, respectively) and two signal-transducing receptor components. Even though IL-6 is expressed by neurons and glia, the functions of IL-6 in the nervous system are poorly understood. Here, we report that exogenous human IL-6 promotes the survival of dissociated newborn rat DRG neurons in vitro if supplemented with soluble human IL-6-alpha-receptor. The dosages of human IL-6 and soluble human IL-6R necessary to achieve neurotrophic effects could be reduced markedly by linking ligand and alpha-receptor component in a designer cytokine. Furthermore, we show that newborn rat DRG neurons express and secrete bioactive IL-6. Endogenously secreted IL-6 does not enhance survival of these neurons in vitro, suggesting that DRG neurons do not sufficiently express cell surface IL-6R. Exogenously added soluble rat IL-6R rendered DRG neurons responsive to secreted IL-6. Our results indicate an autocrine function of IL-6 in DRG neuron survival which depends on membrane-bound or soluble IL-6R as a neurotrophic cofactor.