Differential regulation of type I and type II interleukin-1 receptors in focal brain inflammation.
Most pathologies of the brain have an inflammatory component, associated with the release of cytokines such as interleukin-1beta (IL-1beta) from resident and infiltrating cells. The IL-1 type I receptor (IL-1RI) initiates a signalling cascade but the type II receptor (IL-1RII) acts as a decoy receptor. Here we have investigated the expression of IL-1beta, IL-1RI and IL-1RII in distinct inflammatory lesions in the rat brain. IL-1beta was injected into the brain to generate an inflammatory lesion in the absence of neuronal cell death whereas neuronal death was specifically induced by the microinjection of N-methyl-D-aspartate (NMDA). Using TaqMan RT-PCR and ELISA, we observed elevated de novo IL-1beta synthesis 2 h after the intracerebral microinjection of IL-1beta; this de novo IL-1beta remained elevated 24 h later. There was a concomitant increase in IL-1RI mRNA but a much greater increase in IL-1RII mRNA. Immunostaining revealed that IL-1RII was expressed on brain endothelial cells and on infiltrating neutrophils. In contrast, although IL-1beta and IL-1RI were elevated to similar levels in response to NMDA challenge, the response was delayed and IL-1RII mRNA expression was unchanged. The lesion-specific expression of IL-1 receptors suggests that the receptors are differentially regulated in a manner not directly related to the endogenous level of IL-1 in the CNS.
Docagne
Fabian
F
Molecular Neuropathology Laboratory, School of Biological Sciences, University of Southampton, UK. docagne@cajal.csic.es
Campbell
Sandra J
SJ
Bristow
Adrian F
AF
Poole
Stephen
S
Vigues
Stephan
S
Guaza
Carmen
C
Perry
V Hugh
VH
Anthony
Daniel C
DC
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004660:Encephalitis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D013997:Time Factors
D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D016202:N-Methylaspartate