Nature immunology, 2012-05, Vol.13 (5), p.465-473
2012
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- Autor(en) / Beteiligte
- Titel
- The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss
- Ist Teil von
- Nature immunology, 2012-05, Vol.13 (5), p.465-473
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Aging is linked to greater susceptibility to chronic inflammatory diseases, several of which, including periodontitis, involve neutrophil-mediated tissue injury. Here we found that aging-associated periodontitis was accompanied by lower expression of Del-1, an endogenous inhibitor of neutrophil adhesion dependent on the integrin LFA-1, and by reciprocal higher expression of interleukin 17 (IL-17). Consistent with that, IL-17 inhibited gingival endothelial cell expression of Del-1, thereby promoting LFA-1-dependent recruitment of neutrophils. Young Del-1-deficient mice developed spontaneous periodontitis that featured excessive neutrophil infiltration and IL-17 expression; disease was prevented in mice doubly deficient in Del-1 and LFA-1 or in Del-1 and the IL-17 receptor. Locally administered Del-1 inhibited IL-17 production, neutrophil accumulation and bone loss. Therefore, Del-1 suppressed LFA-1-dependent recruitment of neutrophils and IL-17-triggered inflammatory pathology and may thus be a promising therapeutic agent for inflammatory diseases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1529-2908eISSN: 1529-2916DOI: 10.1038/ni.2260Titel-ID: cdi_pubmed_primary_22447028
- Format
- –
- Schlagworte
- Aging - immunology, Alveolar Bone Loss - immunology, Animals, Calcium-Binding Proteins, Carrier Proteins - immunology, Carrier Proteins - metabolism, Carrier Proteins - pharmacology, Cell Adhesion - drug effects, Cell Adhesion Molecules, Endothelial Cells - drug effects, Endothelial Cells - immunology, Female, Integrins - antagonists & inhibitors, Integrins - immunology, Integrins - metabolism, Intercellular Signaling Peptides and Proteins, Interleukin-17 - antagonists & inhibitors, Interleukin-17 - immunology, Interleukin-17 - metabolism, Lymphocyte Function-Associated Antigen-1 - immunology, Lymphocyte Function-Associated Antigen-1 - metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Neutrophil Infiltration - drug effects, Neutrophil Infiltration - immunology, Neutrophils - immunology, Neutrophils - metabolism, Periodontal Atrophy - immunology, Periodontal Atrophy - metabolism, Periodontitis - immunology, Periodontitis - metabolism, Periodontitis - therapy, Receptors, Interleukin-17 - deficiency, Receptors, Interleukin-17 - metabolism