Trimethyltin-evoked apoptosis of murine hippocampal granule neurons is accompanied by the expression of interleukin-1beta and interleukin-1 receptor antagonist in cells of ameboid phenotype, the majority of which are NG2-positive.
Interleukin-1beta (IL-1beta) has been implicated in various neuropathologies, while IL-1 receptor antagonist (IL-1ra) has been shown to reduce neuronal injury. We investigated the pattern of expression of both cytokines in murine hippocampus after trimethyltin (TMT) intoxication. Using a ribonuclease protection assay, we demonstrated induction of transcription of IL-1beta and IL-1ra 3 days following TMT treatment which correlated with the peak of neuronal apoptosis. At this time, immunocytochemical staining revealed enhanced expression of both cytokines in NG2 proteoglycan expressing ameboid cells located at the site of neurotoxic insult, some of which bound also the microglial marker, lectin. There was some overlap between NG2 and lectin staining. Our results suggest that the two cytokines are involved in apoptotic processes in dentate granule cells and indicate that the pro-apoptotic effect of IL-1beta prevails over the presumed protective action of IL-1ra. The novel finding of expression of both cytokines in NG2(+) cells of ameboid phenotype indicates that these cells, through the regulatory roles of pro- and anti-inflammatory cytokines, may be involved in control of neuronal death or survival after injury.
Fiedorowicz
Anna
A
Laboratory of Mechanisms of Neurodegeneration and Neuroprotection, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Pasteur 3 Street, 02-093 Warsaw, Poland.
Figiel
Izabela
I
Zaremba
Małgorzata
M
Dzwonek
Karolina
K
Schliebs
Reinhard
R
Oderfeld-Nowak
Barbara
B
D000818:Animals; D000941:Antigens / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole / Q000737:chemistry; D002352:Carrier Proteins / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011509:Proteoglycans / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D013997:Time Factors; D014298:Trimethyltin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D006690:Bisbenzimidazole; D002352:Carrier Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D011509:Proteoglycans; D014298:Trimethyltin Compounds; D000099216:Chondroitin Sulfate Proteoglycan 4; C046488:trimethyltin