Premium
IL‐10 and IL‐4 regulate type‐I and type‐II IL‐1 receptors expression on IL‐1β‐activated mouse primary astrocytes
Author(s) -
Pousset F.,
Cremona S.,
Dantzer R.,
Kelley K. W.,
Parnet P.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00569.x
Subject(s) - receptor , inflammation , interleukin , biology , interleukin 1 receptor, type ii , microbiology and biotechnology , cytokine , immunology , biochemistry , interleukin 5
When activated by its ligand, the interleukin receptor type I (IL‐1RI) transduces signals in cooperation with the IL‐1 receptor accessory protein (IL‐1RacP). In contrast, IL‐1RII functions as a decoy receptor without participating in IL‐1 signalling. Brain astrocytes are cellular targets of IL‐1 and play a pivotal role in brain responses to inflammation. The regulation of IL‐1 receptors on astrocytes by anti‐inflammatory cytokines such as IL‐4 and IL‐10 has not been studied, despite its importance for understanding the way these cells respond to IL‐1. Using RT‐PCR, we first showed that the expression of IL‐1RI and IL‐1RII, but not IL‐1RacP, mRNAs are up‐regulated by IL‐1β in a time‐dependent manner. Using a radioligand binding technique, we then showed that astrocytes display an equivalent number of IL‐1RI and IL‐1RII. IL‐1β decreases the number of IL‐1RI binding sites, whereas it increases those of IL‐1RII. IL‐4 and IL‐10 both up‐regulate IL‐1RII IL‐1β‐induced, but only IL‐4 does so for IL‐1RI. At the protein level, IL‐4 and IL‐10 dramatically reverse the ability of IL‐1β to inhibit expression of IL‐1RI but neither affects the ability of IL‐1β to enhance the number of IL‐1RII. Collectively, these results establish the existence of receptor cross‐talk between pro‐ and anti‐inflammatory cytokines on a critical type of cell that regulates inflammatory events in the brain.