title: Cytokines regulate alpha(1)-adrenergic receptor mRNA expression in human monocytic cells and endothelial cells.
abstract: The family of adrenergic receptors (AR) plays a central role in regulation of the activity of many organ systems. Consequently, regulated expression of the various subtypes of AR is an important mechanism in maintaining homeostasis. Previously, we have shown that alpha(1)-AR triggering of peripheral blood mononuclear cells from patients with juvenile chronic arthritis results in increased IL-6 production. In contrast, alpha(1)-AR agonists do not alter cytokine production by cells of healthy individuals. The aim of the present study was to investigate whether pro-inflammatory cytokines can regulate the expression of mRNA encoding AR of the alpha(1)-family. We show that human THP-1 monocytic cells express mRNA encoding of two of the three cloned subtypes of alpha(1)-AR: alpha(1b)-AR and alpha(1d)-AR mRNA. The cytokines TNF-alpha and IL-1beta decrease level of mRNA for alpha(1d)-AR in THP-1 monocytic cells. In contrast, alpha(1b)-AR mRNA levels are not affected by these two cytokines. Interestingly, IL-1beta and TNF-alpha induce the expression of alpha(1a)-AR mRNA in THP-1 monocytic cells. In human umbilical vein endothelial cells (HUVEC), IL-1beta and TNF-alpha decrease both alpha(1b)-AR and alpha(1d)-AR mRNA levels in HUVEC. alpha(1a)-AR mRNA is not detectable in HUVEC.IL-6 and IL-8, two other pro-inflammatory cytokines tested in this study, do not change alpha(1)-AR subtype levels in HUVEC or monocytic cells. Our data demonstrate that TNF-alpha and IL-1beta can regulate expression of alpha(1)-AR mRNA and that cytokine regulation of alpha(1)-AR expression is subtype- and tissue-specific.
authors.affiliation: Laboratory for Psychoneuroimmunology, Department of Immunology, University Medical Center Utrecht, Room KC03.068.0, Lundlaan 6, 3584 EA Utrecht, The Netherlands. c.heijnen@wkz.azu.nl
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rouppe van der Voort
authors.forename: Marion
authors.initials: M
authors.lastname: van de Pol
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D014409:Tumor Necrosis Factor-alpha