title: Prostaglandin E(2) enhances IL-33 production by dendritic cells.
abstract: While interleukin (IL)-33, a novel member of the IL-1 family, seems to promote T helper type 2 (Th2)-associated inflammations and allergic diseases, the stimulating factors for IL-33 production are less well characterized. Prostaglandin E(2) (PGE(2)) has been shown to suppress immune cell functions. However, the immune enhancement by this mediator is not well understood. In the present study, we examined the effect of PGE(2) on IL-33 production by dendritic cells (DCs). Bone marrow-derived DCs were stimulated with lipopolysaccharide (LPS) in the presence or absence of PGE(2). LPS increased mRNA expression of the IL-1 family members, IL-1, IL-18, and IL-33 in DCs. PGE(2) alone showed slight effect on IL-1, IL-18, and IL-33 mRNA expression in DCs. Of note, LPS combined with PGE(2) caused in a synergistic enhancement of mRNA expression of IL-33 but not IL-1 and IL-18. In addition, PGE(2) dramatically enhanced IL-33 protein production by DCs upon LPS stimulation. The protein kinase A (PKA) inhibitor H89 significantly inhibited the PGE(2)-mediated enhancement of IL-33 production by DCs. Thus, PGE(2) appears to enhance IL-33 mRNA expression and its protein synthesis via PKA pathway in DCs. PGE(2) may promote Th2-mediated inflammations through the enhancement of IL-33 production by DCs, which might be associated with the pathogenesis of allergic diseases.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa, Ishikari-Tobetsu, Japan. yanagawa@hoku-iryo-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Momoka
authors.initials: M
authors.lastname: Suzuki
authors.forename: Machiko
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D006967:Hypersensitivity / Q000503:physiopathology; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C506535:Il33 protein, mouse; D020382:Interleukin-18; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone