Interleukin-6-type cytokines in neuroprotection and neuromodulation: oncostatin M, but not leukemia inhibitory factor, requires neuronal adenosine A1 receptor function.
Neuroprotection is one of the prominent functions of the interleukin (IL)-6-type cytokine family, for which the underlying mechanism(s) are not fully understood. We have previously shown that neuroprotection and neuromodulation mediated by IL-6 require neuronal adenosine A(1) receptor (A(1) R) function. We now have investigated whether two other IL-6-type cytokines [oncostatin M (OSM) and leukemia inhibitory factor (LIF)] use a similar mechanism. It is presented here that OSM but not LIF, enhanced the expression of A(1) Rs (both mRNA and protein levels) in cultured neurons. Whereas the neuroprotective effect of LIF was unchanged in A(1) R deficient neurons, OSM failed to protect neurons in the absence of A(1) R. In addition, OSM pre-treatment for 4 h potentiated the A(1) R-mediated inhibition of electrically evoked excitatory post-synaptic currents recorded from hippocampal slices either under normal or hypoxic conditions. No such effect was observed after LIF pre-treatment. Our findings thus strongly suggest that, despite known structural and functional similarities, OSM and LIF use different mechanisms to achieve neuroprotection and neuromodulation.
Moidunny
Shamsudheen
S
Department of Neuroscience, Section Medical Physiology, University Medical Center Groningen (UMCG), Rijksuniversiteit Groningen (RUG), Groningen, the Netherlands.
Dias
Raquel Baptista
RB
Wesseling
Evelyn
E
Sekino
Yuko
Y
Boddeke
Hendrikus W G M
HW
Sebastião
Ana Maria
AM
Biber
Knut
K
D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D053683:Oncostatin M / Q000494:pharmacology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D043682:Receptor, Adenosine A1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D009435:Synaptic Transmission
D053605:Leukemia Inhibitory Factor; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D011994:Recombinant Proteins; D053683:Oncostatin M