A Toll-like receptor 9-mediated pathway stimulates perilipin 3 (TIP47) expression and induces lipid accumulation in macrophages
| Autor: | Bin Fan, Shoichiro Ikuyama, Xiao-Guang Yan, Difei Wang, Jianqiu Gu, Jin Zhang, Wei-Li Zhong |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Physiology Endocrinology Diabetes and Metabolism Blotting Western Biology Cell Line Perilipin-3 Mice Physiology (medical) Internal medicine medicine Animals Receptor Triglycerides Foam cell Toll-like receptor Kinase Reverse Transcriptase Polymerase Chain Reaction Macrophages JNK Mitogen-Activated Protein Kinases TLR9 Chloroquine Atherosclerosis Cell biology Mice Inbred C57BL Endocrinology Biochemistry Oligodeoxyribonucleotides Cell culture Toll-Like Receptor 9 Perilipin RNA Female Carrier Proteins Intracellular |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 299(4) |
| ISSN: | 1522-1555 |
| Popis: | Excessive accumulation of lipids in macrophages results in formation of foam cells and is a hallmark of atherosclerosis. The PAT family of proteins has been implicated in this process, but details of their involvement in foam cell formation have not been fully elucidated. One of dominant members of the PAT proteins, perilipin 3 (TIP47), is likely to be involved in such a regulatory mechanism. In this study, we demonstrated that the Toll-like receptor 9 (TLR9)-mediated pathway stimulates perilipin 3 expression and accumulation of lipids, especially triglycerides, in macrophages. Oligodeoxynucleotide (ODN) 1826, a ligand of TLR9, significantly enhanced perilipin 3 expression in RAW264.7 cells, and chloroquine, a TLR9 inhibitor, almost completely inhibited ODN1826-induced perilipin 3 expression. The inhibitors of c-jun NH2-terminal kinase and PI 3-kinase suppressed the level of perilipin 3 mRNA induced by ODN1826. ODN1826 induced the expression of IL-1α and IFNβ, both of which increased perilipin 3 expression. Antibodies against these cytokines suppressed the ODN1826-induced perilipin 3 mRNA levels. These results suggest that the expression of perilipin 3 in macrophages is in part regulated through the TLR9-mediated mechanism. Furthermore, ODN1826 increased intracellular lipid accumulation in the presence of oxLDL, which was reduced by perilipin 3 siRNA. Perilipin 3 expression was not stimulated by oxLDL. Depletion of perilipin 3 by siRNA specifically reduced triglyceride content in the cells but not cholesterol content, indicating that perilipin 3 is involved mainly in triglyceride accumulation. In conclusion, the TLR9-mediated pathway facilitates foam cell formation in part through increased expression of perilipin 3. |
| Databáze: | OpenAIRE |
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