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Interleukin‐1 Receptor Defect in Autoimmune NZB Mouse Brain
Author(s) -
HAOUR FRANCE,
JAFARIANTEHRANI MEHRNAZ,
GABELLEC MARIEMADELEINE,
CRUMEYROLLEARIAS MICHELE,
HU YANHUA,
WICK GEORG,
TERNYNCK THERESE
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb09614.x
Subject(s) - receptor , immunology , medicine , neuroscience , biology
A bstract : Interleukin‐1 receptors (lL‐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‐1α, β, 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.