title: Downregulating galectin-3 inhibits proinflammatory cytokine production by human monocyte-derived dendritic cells via RNA interference.
abstract: Galectin-3 (Gal-3), a β-galactoside-binding lectin, serves as a pattern-recognition receptor (PRR) of dendritic cells (DCs) in regulating proinflammatory cytokine production. Galectin-3 (Gal-3) siRNA downregulates expression of IL-6, IL-1β and IL-23 p19, while upregulates IL-10 and IL-12 p35 in TLR/NLR stimulated human MoDCs. Furthermore, Gal-3 siRNA-treated MoDCs enhanced IFN-γ production in SEB-stimulated CD45RO CD4 T-cells, but attenuated IL-17A and IL-5 production by CD4 T-cells. Addition of neutralizing antibodies against Gal-3, or recombinant Gal-3 did not differentially modulate IL-23 p19 versus IL-12 p35. The data indicate that intracellular Gal-3 acts as cytokine hub of human DCs in responding to innate immunity signals. Gal-3 downregulation reprograms proinflammatory cytokine production by MoDCs that inhibit Th2/Th17 development.
authors: Department of Immunology, The Institute of Genetics, San Diego, CA, USA; Department of Allergy, Inflammation and Vaccinology, IGE Therapeutics, Inc., San Diego, CA, USA; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: alex@ige-therapeutics.com.
authors: Swey-Shen
authors: SS
authors: Chen
authors: Department of Immunology, The Institute of Genetics, San Diego, CA, USA; Department of Allergy, Inflammation and Vaccinology, IGE Therapeutics, Inc., San Diego, CA, USA.
authors: Liang-Wu
authors: LW
authors: Sun
authors: Department of Immunology, The Institute of Genetics, San Diego, CA, USA; Department of Allergy, Inflammation and Vaccinology, IGE Therapeutics, Inc., San Diego, CA, USA.
authors: Howard
authors: H
authors: Brickner
authors: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors: Pei-Qing
authors: PQ
authors: Sun
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015536:Down-Regulation; D037502:Galectin 3 / Q000096:biosynthesis* / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis; D053765:Interleukin-12 Subunit p35 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D053760:Interleukin-23 Subunit p19 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D051192:Receptors, Pattern Recognition / Q000096:biosynthesis / Q000235:genetics*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D016207:Cytokines; D037502:Galectin 3; C508609:IL10 protein, human; C508585:IL1B protein, human; C508840:IL23A protein, human; C508600:IL6 protein, human; D053765:Interleukin-12 Subunit p35; D053583:Interleukin-1beta; D053760:Interleukin-23 Subunit p19; D015850:Interleukin-6; D034741:RNA, Small Interfering; D051192:Receptors, Pattern Recognition; D016753:Interleukin-10
keywords: Cytokines; Dendritic cells; Galectin-3; Inflammation; Innate immunity; Th17