The interleukin-1-related cytokine IL-1F8 is expressed in glial cells, but fails to induce IL-1beta signalling responses.
The putative new interleukin (IL)-1 family member IL-1F8 (IL-1eta, IL-1H2) has been shown recently to activate mitogen activated protein kinases (MAPKs), extracellular signal-regulated protein kinase (ERK1/2) and c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NFkappa B) via a mechanism that requires IL-1Rrp2 expression in cell lines. The aim of this study was to test the hypothesis that IL-1F8 contributes to brain inflammation and injury, by studying its expression and actions in the different cell types of the mouse brain in culture. Messenger RNA for IL-1F8 was detected in neurons and glia (microglial cells, oligodendrocytes progenitor cells and to a lesser extent astrocytes) by RT-PCR. Bacterial lipopolysaccharide (LPS) had no effect on IL-1F8 mRNA levels in mixed glial cultures. Recombinant mouse IL-1beta induced strong activation of ERK1/2, p38, JNK and NFkappa B, and significant release of IL-6 and PGE2, which was blocked by IL-1ra. In contrast, recombinant mouse IL-1F8 did not influence any of these parameters. These results demonstrate that CNS cells may be a source of IL-1F8, but the failure of LPS to modulate IL-1F8 mRNA expression, and of recombinant IL-1F8 to induce any of the classical IL-1 responses, suggest that this cytokine has restricted activities in the brain, or that it may act via alternative pathway(s).
Wang
Penglian
P
School of Biological Sciences, 1-124 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Meinhardt
Brenda
B
Andre
Ralph
R
Renshaw
Blair R
BR
Kimber
Ian
I
Rothwell
Nancy J
NJ
Pinteaux
Emmanuel
E
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
C502352:IL-1F8 protein, mouse; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone