Suppression of Toll-like Receptor-Mediated Innate Immune Responses at the Ocular Surface by the Membrane-associated Mucins MUC1 and MUC16
| Autor: | Balaraj B. Menon, Christina Kaiser-Marko, Ilene K. Gipson, Ann S. Tisdale, Sandra Spurr-Michaud |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Conjunctiva
Immunology Biology Article Proinflammatory cytokine Cornea 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Animals Humans 030304 developmental biology Corneal epithelium Cell Line Transformed Mice Knockout 0303 health sciences Toll-like receptor Innate immune system Mucin-1 Membrane Proteins Listeria monocytogenes Epithelium eye diseases Immunity Innate Toll-Like Receptor 2 TLR2 Toll-Like Receptor 5 medicine.anatomical_structure TLR5 CA-125 Antigen Cytokines sense organs 030215 immunology |
| Zdroj: | Mucosal immunology |
| ISSN: | 1935-3456 1933-0219 |
| Popis: | Membrane-associated mucins (MAMs) expressed on the ocular surface epithelium form a dense glycocalyx that is hypothesized to protect the cornea and conjunctiva from external insult. In this study, the hypothesis that the MAMs MUC1 and MUC16, expressed on the apical surface of the corneal epithelium, suppress Toll-like receptor (TLR)-mediated innate immune responses was tested. Using an in vitro model of corneal epithelial cells that are cultured to express MAMs, we show that reduced expression of either MUC1 or MUC16 correlates with increased message and secreted protein levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) following exposure of cells to the TLR2 and TLR5 agonists, heat-killed Listeria monocytogenes and flagellin, respectively. As mice express Muc1 (but not Muc16) in the corneal epithelium, a Muc1(-/-) mouse model was used to extend in vitro findings. Indeed, IL-6 and TNF-α message levels were increased in the corneal epithelium of Muc1(-/-) mice, in comparison with wild-type mice, following exposure of enucleated eyes to the TLR2 and TLR5 agonists. Our results suggest that the MAMs MUC1 and MUC16 contribute to the maintenance of immune homeostasis at the ocular surface by limiting TLR-mediated innate immune responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink