Glucocorticoid upregulation of interleukin 1 receptor expression in a glioblastoma cell line.
Interleukin 1 (IL-1) is a multifunctional cytokine produced by numerous cell types, including cells of the central nervous system (CNS). In the CNS, IL-1 produced by glia is thought to support trophic functions after brain injury. However, little is known about whether the IL-1 receptor (IL-1R) is expressed in brain cells and how these receptors might be regulated. Analysis of IL-1R expression in the human glioblastoma cell line U-87 MG indicated the presence of a specific, saturable, and high-affinity (dissociation constant = 104 +/- 14 pM) binding site, which was of moderately high density (1,228 +/- 156 sites/cell). Incubation of U-87 MG cells with cortisol or dexamethasone for as little as 6 h resulted in an upregulation of IL-1R expression, which could be blocked by coincubation with cycloheximide or actinomycin D. IL-1 beta downregulated the expression of its own binding site. Upregulation of the IL-1R by glucocorticoids (GCs) appeared to be coupled to the release of interleukin 6 (IL-6), since IL-1 was significantly more potent in inducing IL-6 release in U-87 cells that were preincubated in the presence of GCs compared with cells incubated in the absence of GCs. These results suggest that IL-1 acts on glial cells via a high-affinity receptor and indicate that GCs may amplify or prolong the actions of IL-1 in the CNS.
Gottschall
P E
PE
US-Japan Biomedical Research Laboratories, Tulane University, Hebert Center, Belle Chasse, Louisiana.
Koves
K
K
Mizuno
K
K
Tatsuno
I
I
Arimura
A
A
D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005910:Glioma; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D007700:Kinetics; D011971:Receptors, Immunologic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D015854:Up-Regulation / Q000187:drug effects
D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D015850:Interleukin-6; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; D006854:Hydrocortisone