Premium
Interleukin‐6 (IL‐6) and its soluble receptor support survival of sensory neurons
Author(s) -
Thier M.,
März P.,
Otten U.,
Weis J.,
RoseJohn S.
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990215)55:4<411::aid-jnr2>3.0.co;2-d
Subject(s) - ciliary neurotrophic factor , receptor , neurotrophic factors , microbiology and biotechnology , biology , neurotrophin , autocrine signalling , cytokine , dorsal root ganglion , neuron , neuroscience , medicine , immunology , sensory system , biochemistry
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 α‐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‐α‐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 α‐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. J. Neurosci. Res. 55:411–422, 1999. © 1999 Wiley‐Liss, Inc.