Interleukin-1 receptor defect in autoimmune NZB mouse brain.
Interleukin-1 receptors (IL-1R type I and II) have been characterized in murine nervous structures (hippocampus and frontal cortex), in vascular structures (vessels, choroid plexus), and in the anterior pituitary. Because interleukin-1 (IL-1), injected or induced in the brain, is a powerful regulator of the stress axis and immune functions, it was of interest to investigate IL-1Rs and IL-1 in autoimmune mice. In control mice, bacterial lipopolysaccharide (LPS), administered i.p. or i.c.v., induces a sharp decrease in available brain IL-1 receptors, in spite of a moderate increase in mRNAs for both receptor types. This is concomitant with an increase in IL-1 alpha, beta, and ra mRNA. Ligand production clearly overcomes receptor turnover. In autoimmune mice (NZB and NZB/NZW F1), a strong defect in IL-1R (type I) is demonstrated in the dentate gyrus. This tissue-specific defect cannot be explained by increased occupancy by endogeneous ligands as for LPS-treated mice. The transmission of the defect is Mendelian and suggests the involvement of a single gene. However patterns of IL-1R mRNAs (evaluated by RT-PCR) are similar in NZB and in controls, suggesting a translational or post-translational abnormality. The contribution of this genetic disorder in the development of autoimmunity remains to be clarified. Because the brain IL-1 system sends inhibitory signals towards immune functions, this lack of functional IL-1 binding sites might participate in the disregulations observed in NZB autoimmune mice.
Haour
F
F
Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France.
Jafarian-Tehrani
M
M
Gabellec
M M
MM
Crumeyrolle-Arias
M
M
Hu
Y
Y
Wick
G
G
Ternynck
T
T
D000818:Animals; D015551:Autoimmunity / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008814:Mice, Inbred NZB / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1