title: Induction of macrophage scavenger receptor type BI expression by tamoxifen and 4-hydroxytamoxifen.
abstract: OBJECTIVE
  Scavenger receptor type BI (SR-BI) is an HDL receptor that is expressed by macrophages. SR-BI expression is tightly linked to the development of atherosclerosis. Tamoxifen has been shown to be atheroprotective. However, the involved mechanisms have not been fully elucidated.
  
  
  RESULTS
  In this study, we investigated the effect of tamoxifen and 4-hydroxytamoxifen on macrophage SR-BI expression. Macrophage cell lines and peritoneal macrophages isolated from wild-type mice were used to determine changes in SR-BI mRNA and protein expression in response to tamoxifen and 4-hydroxytamoxifen. We observed that tamoxifen and 4-hydroxytamoxifen increased SR-BI protein expression in a macrophage cell line derived from female mice (J774 cells) but not in a line derived from male mice (RAW cells). Similar observations were obtained in primary macrophages isolated from wild-type male and female mice. Thus, the induction of macrophage SR-BI expression by tamoxifen and 4-hydroxytamoxifen is sex-dependent. Furthermore, we observed that SR-BI expression was induced by activating the oestrogen receptor (ER, specifically ERα) but was inhibited by inactivating the ER. However, the increased macrophage SR-BI protein expression was independent of transcription because SR-BI mRNA expression and promoter activity were not influenced by tamoxifen and 4-hydroxytamoxifen. Instead, tamoxifen increased the stability of macrophage SR-BI protein. Tamoxifen administration to mice had no effect on hepatic SR-BI protein expression but improved the serum lipid profile.
  
  
  CONCLUSIONS
  Our study demonstrates that tamoxifen and 4-hydroxytamoxifen induce macrophage SR-BI protein expression via a post-transcriptional mechanism.
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Pengzhi
authors.initials: P
authors.lastname: Dong
authors.forename: Tao
authors.initials: T
authors.lastname: Xie
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Zhou
authors.forename: Wenquan
authors.initials: W
authors.lastname: Hu
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Chen
authors.forename: Yajun
authors.initials: Y
authors.lastname: Duan
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.forename: Jihong
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D004965:Estrogen Antagonists; D008055:Lipids; D012333:RNA, Messenger; D051116:Receptors, Scavenger; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C016601:afimoxifene