title: Oxysterols induce transition of monocytic cells to phenotypically mature dendritic cell-like cells.
abstract: Dendritic cells (DCs) activate adaptive immune responses in atherosclerotic plaques; however, the origin of DCs is in question. We attempted to determine whether cholesterol or its oxide forms, which are detected in abundance in atheromatous lesions, could induce differentiation or transition of monocytic cells to DCs. Treatment of THP-1 cells with 27-hydroxycholesterol (27OH-Chol) and 7α-hydroxycholesterol (7αOH-Chol) resulted in an increase in the numbers of adherent cells, and, in contrast to PMA, decreased uptake of FITC-conjugated dextran. In addition, treatment with 27OH-Chol and 7αOH-Chol induced expression of mDC-specific molecules, including CD40, CD80, CD83, and CD88. Of the two oxysterols, 27OH-Chol enhanced expression of MHC class I and II molecules as well as CCR7. However, treatment with an identical concentration of cholesterol and 7-ketocholesterol did not influence adherence, uptake of FITC-conjugated dextran, and expression of the aforementioned molecules. This is the first study to report on change of monocytic cells by oxysterols to phenotypically atypical cells with some characteristics of mDCs detected in atherosclerotic lesions. We propose that a certain type of oxysterol would contribute to immune responses in atherosclerotic lesions by enhancing expression of multiple CD molecules as well as MHC molecules by monocytic cells.
authors.affiliation: Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Yonghae
authors.initials: Y
authors.lastname: Son
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Sae-A
authors.initials: SA
authors.lastname: Lee
authors.forename: Seong-Kug
authors.initials: SK
authors.lastname: Eo
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D010641:Phenotype
chemical_list: D006888:Hydroxycholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; C076996:27-hydroxycholesterol
keywords: Atherosclerosis; Dendritic cells; Monocytes; Oxysterols