title: TLR3-dependent immune regulatory functions of human mesangial cells.
abstract: In glomerulonephritis, the migration of inflammatory cells into the glomerulus is an important step in disease initiation and progression. The viral receptor Toll-like receptor 3 (TLR3) is known to play a role in virus-associated glomerulonephritis. Based on this knowledge, this study aimed to define the effects of the TLR3 ligand polyriboinosinic:polyribocytidylic acid (poly(I:C)) on the expression of adhesion molecules and macrophage colony-stimulating factor (M-CSF) on resident glomerular cells. Experiments in MCs demonstrated that the activation of viral receptors by poly(I:C) leads to a time- and dose-dependent induction of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and M-CSF at both the mRNA and protein levels; these results were confirmed by incubating MCs with HCV RNA. As shown in knockdown experiments, this effect is specifically mediated by TLR3. The prestimulation of MCs with proinflammatory cytokines increases the effects of poly(I:C), except for its induction of VCAM-1. Tumor-necrosis factor (TNF)-α, likewise, induces ICAM-1, VCAM-1 and M-CSF, and amplifies the mesangial response to poly(I:C). These results were confirmed by incubating MCs with HCV RNA. We thus provide evidence that human MCs represent a potential target of the leukocytes and monocytes that infiltrate the glomerulus in viral disease-associated GN, highlighting the possibility that MCs may act as resident antigen-presenting cells.
authors.affiliation: Medizinische Poliklinik-Campus Innenstadt, Klinikum der LMU, Pettenkoferstrasse 8a, Munich, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Merkle
authors.forename: Andrea
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Simone
authors.initials: S
authors.lastname: Köppel
authors.forename: Joachim
authors.initials: J
authors.lastname: Pircher
authors.forename: Hanna
authors.initials: H
authors.lastname: Mannell
authors.forename: Maximilian
authors.initials: M
authors.lastname: Roeder
authors.forename: Markus
authors.initials: M
authors.lastname: Wörnle
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D002478:Cells, Cultured; D005921:Glomerulonephritis / Q000276:immunology* / Q000821:virology*; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D050527:Mesangial Cells / Q000276:immunology* / Q000821:virology*; D011070:Poly I-C / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D012367:RNA, Viral; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016173:Macrophage Colony-Stimulating Factor; D011070:Poly I-C