title: Induction of high-affinity interleukin 1 receptor on human peripheral blood lymphocytes by glucocorticoid hormones.
abstract: The in vitro effect of glucocorticoids (GCs) on IL-1-R expression of human PBMCs was investigated. Both physiological and pharmacological concentration ranges of GC increased the specific binding of 125I-labeled human rIL-1 alpha to PBMCs. This enhancement was specific for GC, since other steroid hormones, such as progesterone, 17 beta-estradiol, and testosterone failed to elevate the binding of 125I-IL-1 alpha to PBMCs. The effect was time dependent with maximal effect occurring 6 h after treatment and dose dependent with half-maximal effect elicited by 100 nM prednisolone. Scatchard plot analysis indicated that 125I-IL-1 alpha binding increased from approximately 100 IL-1-R per cell to 2 X 10(3) receptors per cell without a major change in affinity (Kd = 2.6 X 10(-10) M). The subpopulation of PBMCs induced by GC to express higher levels of IL-1-R consisted predominantly of B lymphocytes, but not T lymphocytes, large granular lymphocytes, or monocytes. GCs also induced the expression of IL-1-R on some other cell types, including normal human dermal fibroblasts and the human large granular lymphocyte cell line YT. Since cycloheximide and actinomycin D inhibited the induction of IL-1-R by GC, synthesis of both new RNA and protein seems to be required for IL-1-R induction. This study presents the first evidence of upregulation of the receptors for IL-1 by GC, and may account for the reported enhancement of in vitro and in vivo humoral immune responses by GCs.
authors.affiliation: Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, Maryland 21701.
authors.forename: T
authors.initials: T
authors.lastname: Akahoshi
authors.forename: J J
authors.initials: JJ
authors.lastname: Oppenheim
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000378:metabolism; D017472:Receptors, Interleukin-1; D013268:Stimulation, Chemical
chemical_list: D005938:Glucocorticoids; D012739:Gonadal Steroid Hormones; D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D003609:Dactinomycin; D003513:Cycloheximide