IL-15 aggravates atherosclerotic lesion development in LDL receptor deficient mice
| Autor: | Gijs H.M. van Puijvelde, Theo J.C. Van Berkel, Eva J.A. van Wanrooij, Niels Peterse, Paula de Vos, Thomas van Es, Johan Kuiper, Ingrid N. Michon |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_treatment Spleen Inflammation Biology Mouse model DNA vaccination Lesion Mice Immunology and Microbiology(all) Leukocytes medicine Animals Chemokine CCL2 Interleukin-15 General Veterinary General Immunology and Microbiology Tumor Necrosis Factor-alpha Vaccination Public Health Environmental and Occupational Health Atherosclerosis veterinary(all) medicine.anatomical_structure Cytokine Infectious Diseases Receptors LDL Interleukin 15 LDL receptor Immunology Molecular Medicine Tumor necrosis factor alpha medicine.symptom |
| Zdroj: | Vaccine Vaccine, 29(5), 976-983 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2010.11.037 |
| Popis: | Background Interleukin 15 (IL-15) is a pro-inflammatory cytokine involved in inflammatory diseases and IL-15 is expressed in atherosclerotic plaques. Methods To establish the role of IL-15 in atherosclerosis we studied the effect of IL-15 on atherosclerosis associated cells in vitro and in vivo by neutralizing IL-15 using a DNA vaccination strategy. Results Upon feeding a Western type diet LDLr−/− mice do express higher levels of IL-15 within the spleen and the number of IL-15 expressing cells among blood leukocytes and spleen cells is increased. Addition of IL-15 to macrophages induces the expression TNF-α and CCL-2. After the mice were vaccinated against IL-15, we observe a reduction in plaque size of 75% plaque. Unexpectedly, the relative number of macrophages within the plaque was 2-fold higher in IL-15 vaccinated mice than in control mice. Vaccination against IL-15 leads to an increased cytotoxicity against IL-15 overexpressing target cells, resulting in a reduction in IL-15 expressing cells and macrophages in blood and spleen and a decreased CD4/CD8 ratio. Conclusion Hypercholesterolemia leads to upregulation of IL-15 within spleen and blood. DNA vaccination against IL-15 does markedly reduces atherosclerotic lesion size, but does not promote lesion stability. |
| Databáze: | OpenAIRE |
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