Reciprocal actions of interleukin-6 and brain-derived neurotrophic factor on rat and mouse primary sensory neurons.
In low-density, serum-free cultures of neurons from embryonic rat dorsal root ganglia, interleukin-6 supports the survival of less than one third of the neurons yet virtually all of them bear interleukin-6 alpha-receptors. A finding that might explain this selectivity is that interleukin-6 acts on sensory neurons in culture through a mechanism requiring endogenous brain-derived neurotrophic factor. Antibodies or a trkB fusion protein that block the biological activity of brain-derived neurotrophic factor synthesized by dorsal root ganglion neurons also block the survival-promoting actions of interleukin-6 on these neurons. Two results indicate that interleukin-6 influences synthesis of brain-derived neurotrophic factor in adult dorsal root ganglion neurons. Intrathecal infusion of interleukin-6 in rats increases the concentration of brain-derived neurotrophic factor mRNA in rat lumbar dorsal root ganglia. The induction of brain-derived neurotrophic factor in dorsal root ganglion neurons that is seen after nerve injury in rats or wild-type mice is severely attenuated in mice with null mutation of the interleukin-6 gene. In brief, the ability of interleukin-6 to support the survival of embryonic sensory neurons in vitro depends upon the presence of endogenous brain-derived neurotrophic factor and the induction of brain-derived neurotrophic factor in injured adult sensory neurons depends upon the presence of endogenous interleukin-6.
Murphy
P G
PG
Division of Neurosurgery, Montreal General Hospital and McGill University, Montreal, Canada.
Borthwick
L A
LA
Altares
M
M
Gauldie
J
J
Kaplan
D
D
Richardson
P M
PM
D000367:Age Factors; D000818:Animals; D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D005727:Ganglia, Spinal / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019947:Receptors, Interleukin-6 / Q000378:metabolism
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6