The interleukin-1 type I receptor is expressed in human hypothalamus.
Several lines of evidence suggest that interleukin-1 (IL-1) acts directly on the central nervous system, probably within the hypothalamus, causing effects such as fever, activation of the immune response and sickness behaviour. IL-1 has also been shown to be involved in the aetiology of several neuronal diseases, including neurodegeneration, stroke and Alzheimer's disease. However, the question as to whether the full-length type I IL-1 receptor (IL-1RI) is expressed in the human hypothalamus has yet to be addressed. Using the polymerase chain reaction, we cloned a full-length cDNA encoding the human hypothalamic IL-1RI from human hypothalamic cDNA. The DNA sequence of the human hypothalamic receptor was identical to that of the human fibroblast IL-1RI. The IL-1RI receptor protein was detected in astrocytes of normal human hypothalamic brain sections using immunocytochemical techniques. To ascertain that the cloned receptor was functional, Chinese hamster ovary (CHO) cells were transfected with a plasmid vector containing the IL-1RI coding region. IL-1RI-mediated-signal transduction was assessed by microphysiometry and activation of p38 MAP (mitogen-activated protein) kinase. We report the first demonstration that both the type I IL-1 transcript and the protein are expressed in the human hypothalamus. The receptor was expressed in a stable CHO cell line, providing a tool with which to embark on a thorough analysis of the signalling mechanisms mediated by IL-1 via this receptor.
Hammond
E A
EA
Parke-Davis Neuroscience Research Centre, Cambridge University and School of Biological Sciences, Manchester, UK. Elizabeth.Hammond@wl.com
Smart
D
D
Toulmond
S
S
Suman-Chauhan
N
N
Hughes
J
J
Hall
M D
MD
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000276:immunology; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases; D011869:Radioligand Assay; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D018076:DNA, Complementary; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases