title: Adrenoceptor-mediated enhancement of interleukin-33 production by dendritic cells.
abstract: While noradrenaline and adrenaline suppress some aspects of immune functions, the immune enhancement via these catecholamines is not well understood. Interleukin (IL)-33, a novel member of the IL-1 family, promotes T helper type 2 (T(h)2)-associated inflammations and plays a role in allergic diseases. However, the precise immune cell source and the stimulating factors for IL-33 production are less well characterized. In the present study, we examined the effects of noradrenaline and adrenaline, stress-related catecholamines, on IL-33 production by dendritic cells (DCs). Murine bone marrow-derived DCs were stimulated with lipopolysaccharide (LPS) in the presence or absence of these catecholamines. LPS alone slightly increased IL-33 production by DCs. Noradrenaline or adrenaline dramatically enhanced IL-33 mRNA expression and its protein synthesis by DCs upon LPS stimulation. The noradrenaline-induced enhancement of IL-33 production was completely blocked by β(2)-adrenoceptor specific antagonist ICI 118,551, while β(2)-adrenoceptor specific agonist salmeterol enhanced DC production of IL-33. Protein kinase A (PKA) specific inhibitor H89 blocked the noradrenaline-induced IL-33 production. Cyclic adenosine monophosphate (cAMP) and its analogue enhanced DC production of IL-33 upon LPS stimulation. Thus, β(2)-adrenoceptor-mediated cAMP-PKA pathway appears to enhance DC production of IL-33. The adrenoceptor-mediated enhancement of IL-33 production by DCs might be associated with the stress-related progression of T(h)2-associated disorders.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 060-0293, Japan. yanagawa@hoku-iryo-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Machiko
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D000068299:Salmeterol Xinafoate
chemical_list: D018663:Adrenergic Agents; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D009638:Norepinephrine; D004837:Epinephrine