The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth.
Lesioning the peripheral branch of a dorsal root ganglion (DRG) neuron before injury of the central branch of the same neuron enables spontaneous regeneration of these spinal axons. This effect is cAMP and transcription dependent. Here, we show that the cytokine interleukin-6 (IL-6) is upregulated in DRG neurons after either a conditioning lesion or treatment with dibutyryl-cAMP. In culture, IL-6 allows neurons to grow in the presence of inhibitors of regeneration present in myelin. Importantly, intrathecal delivery of IL-6 to DRG neurons blocks inhibition by myelin both in vitro and in vivo, effectively mimicking the conditioning lesion. Blocking IL-6 signaling has no effect on the ability of cAMP to overcome myelin inhibitors. Consistent with this, IL-6-deficient mice respond to a conditioning lesion as effectively as wild-type mice. We conclude that IL-6 can mimic both the cAMP effect and the conditioning lesion effect but is not an essential component of either response.
Cao
Zixuan
Z
Department of Biological Sciences, Hunter College, The City University of New York, New York, New York 10021, USA.
Gao
Ying
Y
Bryson
J Barney
JB
Hou
Jianwei
J
Chaudhry
Nagarathnamma
N
Siddiq
Mustafa
M
Martinez
Jennifer
J
Spencer
Tim
T
Carmel
Jason
J
Hart
Ronald B
RB
Filbin
Marie T
MT
D000818:Animals; D000831:Animals, Newborn; D003994:Bucladesine / Q000494:pharmacology; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D006131:Growth Inhibitors; D015850:Interleukin-6; D009185:Myelin Proteins; D003994:Bucladesine