27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes
Autor: | Bo-Young Kim, Koanhoi Kim, Sun-Mi Kim, Yungdae Yun, Seong-Kug Eo, Sae-A Lee, Chi-Dae Kim |
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Rok vydání: | 2014 |
Předmět: |
Apolipoprotein E
Chemokine Receptors CCR5 Lymphocyte Mice Transgenic Diet High-Fat Toxicology CXCR3 Jurkat cells Jurkat Cells Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Chemokine receptor Cell Movement Cell Line Tumor polycyclic compounds medicine Animals Humans Phosphorylation Chemokine CCL4 Protein kinase B Chemokine CCL3 Pharmacology biology Th1 Cells Hydroxycholesterols Up-Regulation Cell biology Mice Inbred C57BL Disease Models Animal Cholesterol medicine.anatomical_structure chemistry 27-Hydroxycholesterol biology.protein lipids (amino acids peptides and proteins) Proto-Oncogene Proteins c-akt Signal Transduction |
Zdroj: | Toxicology and Applied Pharmacology. 274:462-470 |
ISSN: | 0041-008X |
Popis: | Th1 lymphocytes are predominant in atherosclerotic lesions. However, mechanisms involved in the Th1 predominance are unknown. We have investigated the possibility of Th1 lymphocyte recruitment in a cholesterol-rich milieu. A high cholesterol diet resulted in enhanced expression of CCR5 ligands, including CCL3 and CCL4, but not of proatherogenic CXCR3 ligands, in atherosclerotic arteries of ApoE(-/-) mice. 27-Hydroxycholesterol and 7α-hydroxycholesterol, cholesterol oxides (oxysterols) detected in abundance in atherosclerotic lesions, greatly induced the transcription of CCL3 and CCL4 genes in addition to enhancing secretion of corresponding proteins by THP-1 monocytic cells. However, an identical or even higher concentration of cholesterol, 7β-hydroxycholesterol, and 7-ketocholsterol did not influence expression of these chemokines. Conditioned media containing the CCR5 ligands secreted from THP-1 cells induced migration of Jurkat T cells expressing CCR5, a characteristic chemokine receptor of Th1 cells, but not of Jurkat T cells that do not express CCR5. The migration of CCR5-expressing Jurkat T cells was abrogated in the presence of a CCR5-neutralizing antibody. 27-Hydroxycholesterol and 7α-hydroxycholesterol enhanced phosphorylation of Akt. Pharmacological inhibitors of phosphoinositide-3-kinase/Akt pathways blocked transcription as well as secretion of CCL3 and CCL4 in conjunction with attenuated migration of CCR5-expressing Jurkat T cells. This is the first report on the involvement of cholesterol oxides in migration of distinct subtype of T cells. We propose that 27-hydroxycholesterol and 7α-hydroxycholesterol can trigger a sequence of events that leads to recruitment of Th1 lymphocytes and phosphoinositide-3-kinase/Akt pathways play a major role in the process. |
Databáze: | OpenAIRE |
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