Identification of a truncated IL-18R beta mRNA: a putative regulator of IL-18 expressed in rat brain.
Interleukin (IL)-18, a member of the IL-1 family, is a key mediator of peripheral inflammation and host defense responses, and has been implicated in inflammatory and neurodegenerative diseases in the brain. IL-18 acts via a receptor complex that closely resembles that of IL-1, consisting of a ligand binding protein, IL-18Ralpha, and an accessory protein, IL-18Rbeta. Here, we describe the presence of a splice variant of IL-18Rbeta that is predicted to encode a truncated soluble protein, consisting of only the first immunoglobulin-like domain of IL-18Rbeta (EMBL/Genbank accession number AJ550893). Both forms of IL-18Rbeta were expressed in rat cortex, striatum, hypothalamus, hippocampus, and also liver, and were detected in pure cultures of microglia, astrocytes and neurons. This novel splice variant is up-regulated rapidly in microglial cells by bacterial lipopolyssacharide (LPS). We propose that this putative truncated form of IL-18Rbeta is analogous to the soluble form of IL-1R accessory protein, and could act as an important regulator of IL-18 actions.
Andre
Ralph
R
School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Wheeler
Rachel D
RD
Collins
Peter D
PD
Luheshi
Giamal N
GN
Pickering-Brown
Stuart
S
Kimber
Ian
I
Rothwell
Nancy J
NJ
Pinteaux
Emmanuel
E
D017398:Alternative Splicing / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D020382:Interleukin-18 / Q000096:biosynthesis / Q000378:metabolism*; D053728:Interleukin-18 Receptor beta Subunit; D008297:Male; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018123:Receptors, Interleukin / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D017384:Sequence Deletion; D012995:Solubility
C486426:Il18rap protein, rat; D020382:Interleukin-18; D053728:Interleukin-18 Receptor beta Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin