title: Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization.
abstract: Pollen grains induce allergies in susceptible individuals by release of allergens upon contact with mucosal membranes of the upper respiratory tract. We recently demonstrated that pollen not only function as allergen carriers but also as rich sources of bioactive lipids that attract cells involved in allergic inflammation such as neutrophils and eosinophils. Here we demonstrate that soluble factors from birch (Betula alba L.) pollen activate human dendritic cells (DCs) as documented by phenotypical and functional maturation and altered cytokine production. Betula alba L. aqueous pollen extracts (Bet.-APE) selectively inhibited interleukin (IL)-12 p70 production of lipopolysaccharide (LPS)- or CD40L-activated DC, whereas IL-6, IL-10, and TNFalpha remained unchanged. Presence of Bet.-APE during DC activation resulted in DC with increased T helper type 2 (Th2) cell and reduced Th1 cell polarizing capacity. Chemical analysis of Bet.-APE revealed the presence of phytoprostanes (dinor isoprostanes) with prostaglandin E(1)-, F(1)-, A(1)-, or B(1)-ring systems of which only E(1)-phytoprostanes dose dependently inhibited the LPS-induced IL-12 p70 release and augmented the Th2 cell polarizing capacity of DC. These results suggest that pollen-derived E(1)-phytoprostanes not only resemble endogenous prostaglandin E(2) structurally but also functionally in that they act as regulators that modulate human DC function in a fashion that favors Th2 cell polarization.
authors.affiliation: ZAUM-Center for Allergy and Environment, Division of Environmental Dermatology and Allergy GSF/TUM, Universität München, 80802 Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Traidl-Hoffmann
authors.forename: Valentina
authors.initials: V
authors.lastname: Mariani
authors.forename: Hubertus
authors.initials: H
authors.lastname: Hochrein
authors.forename: Kathrin
authors.initials: K
authors.lastname: Karg
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Mueller
authors.forename: Thilo
authors.initials: T
authors.lastname: Jakob
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
mesh_terms: D029662:Betula; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000032:analysis / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D028421:Isoprostanes / Q000032:analysis / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear; D011058:Pollen / Q000737:chemistry / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D003517:Cyclopentanes; D005231:Fatty Acids, Unsaturated; D028421:Isoprostanes; C486066:phytoprostane F1; D018664:Interleukin-12
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