U1 RNA induces innate immunity signaling
| Autor: | Eric L. Greidinger, Robert A. Ortmann, Rebecca L. Jorgenson, Michael L. Misfeldt, Mark F. Foecking, Tal Gazitt, Steven L. Young, Robert W. Hoffman |
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| Rok vydání: | 2004 |
| Předmět: |
Immunology
Connective tissue Receptors Cell Surface Biology Ligands medicine.disease_cause Article Cell Line Ribonucleoprotein U1 Small Nuclear Autoimmunity Mice Rheumatology Immunity DNA-directed RNA interference RNA Small Nuclear medicine Animals Humans Immunology and Allergy Pharmacology (medical) Mice Knockout Membrane Glycoproteins Innate immune system Interleukin-6 Interleukin-8 Toll-Like Receptors RNA Immunity Innate Toll-Like Receptor 3 Cell biology Mice Inbred C57BL Toll-Like Receptor 5 medicine.anatomical_structure Cell Division Signal Transduction |
| Zdroj: | Arthritis & Rheumatism. 50:2891-2896 |
| ISSN: | 1529-0131 0004-3591 |
| Popis: | The U1-70-kd RNP is a prominent target of autoimmunity in connective tissue diseases. In this study, we explored whether its endogenous ligand, U1 RNA, mediates a proimmune signal and may be immunogenic.We assayed the proliferation of control and MyD88-knockout splenocytes in response to in vitro-synthesized U1 RNA, and measured interleukin-6 (IL-6) and IL-8 secretion induced by U1 RNA in a human cell line competent for signaling through Toll-like receptor 3 (TLR-3) and TLR-5.Treatment with U1 RNA or with poly(I-C), a known agonist of TLR-3, induced approximately twice as much control splenocyte proliferation as did treatment with RNase-digested U1 RNA. Proliferation in response to either poly(I-C) or U1 RNA by MyD88-knockout splenocytes was similarly attenuated. Similar to poly(I-C), U1 RNA induced significant secretion of both IL-6 and IL-8 from a TLR-3-expressing human cell line; in contrast, the TLR-5 agonist flagellin induced predominantly IL-8 secretion. Pretreatment of U1 RNA with RNase abolished IL-6 and IL-8 secretion.U1 RNA is capable of inducing manifestations consistent with TLR-3 activation. The ability of U1 RNA (which has a substantial double-stranded secondary structure) to activate TLR-3 may contribute to the immunogenicity of the U1-70-kd autoantigen. Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins. |
| Databáze: | OpenAIRE |
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