title: Up-regulation of galectin-9 induces cell migration in human dendritic cells infected with dengue virus.
abstract: Galectin-9 (Gal-9) exerts immunosuppressive effects by inducing apoptosis in T cells that produce interferon-γ and interleukin (IL)-17. However, Gal-9 can be pro-inflammatory in lipopolysaccharide-stimulated monocytes. Using microarray analysis, we observed that Gal-9 was up-regulated in human dendritic cells (DCs) after dengue virus (DV) infection. The investigation into the immunomodulatory effects and mechanisms of Gal-9 in DCs exposed to DV revealed that DV infection specifically increased mRNA and protein levels of Gal-9 but not those of Gal-1 or Gal-3. Blocking p38, but not c-Jun N-terminal kinase or extracellular signal-regulated kinase (ERK), inhibited DV-induced expression of Gal-9. Reduction in Gal-9 by small interference RNA treatment suppressed DV-stimulated migration of DCs towards the chemoattractants CCL19 and CCL21. In addition, DV-induced IL-12p40 production was reduced after knockdown of Gal-9 in DCs. Furthermore, Gal-9 deficiency suppressed DV-induced activation of nuclear factor-κB. Inhibition of DV-induced DC migration under conditions of Gal-9 deficiency was mediated through suppressing ERK activation but not by regulating the expression of CCR7, the receptor for CCL19 and CCL21. Both the reduction in IL-12 production and the suppression of ERK activity might account for the inhibition of DV-induced DC migration after knockdown of Gal-9. In summary, this study reveals the roles of Gal-9 in DV-induced migration of DCs. The findings indicate that Gal-9 might be a therapeutic target for preventing immunopathogenesis induced by DV infection.
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Hsu
authors.forename: Mei-Yi
authors.initials: MY
authors.lastname: Wang
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Ho
authors.forename: Chuan-Yueh
authors.initials: CY
authors.lastname: Huang
authors.forename: Jenn-Haung
authors.initials: JH
authors.lastname: Lai
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000378:metabolism; D054421:Chemokine CCL21 / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D003716:Dengue Virus / Q000254:growth & development* / Q000502:physiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D037161:Galectins / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D054415:Chemokine CCL19; D054421:Chemokine CCL21; D004791:Enzyme Inhibitors; D037161:Galectins; D007093:Imidazoles; D053762:Interleukin-12 Subunit p40; C105032:LGALS9 protein, human; D016328:NF-kappa B; D011725:Pyridines; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: cell migration; dendritic cells; dengue virus; galectin-9; immune response; mitogen-activated protein kinase