Effect of tacrolimus on the expression of macrophage scavenger and nuclear hormone receptors in THP-1-derived human macrophages

Song Jin, A. Scott Mathis, Kevin Gioia, Tamara Minko, Gary S. Friedman, Joseph Rosenblatt, Felice Peng, David S. Serur, Gregory T. Knipp

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background. Data indicate that tacrolimus and cyclosporine A (CsA) differentially affect the risk of atherosclerosis. The results of our recent in vitro studies of clinically relevant CsA concentrations demonstrated the modulation of macrophage scavenger receptors (MSRs) involved in atherogenesis. This work evaluated the effects of clinically relevant tacrolimus concentrations on the expression of the MSR genes CD36 and CD68, SR-A and SR-BII, lectin-like oxidized low-density lipoprotein receptor-1, the nuclear hormone receptors peroxisome proliferator-activated receptor (PPAR)γ and liver-X-receptor-α, and the cholesterol efflux pump ABCA1 in the in vitro human THP-1 macrophage model. Methods. The cells were cultured and differentiated into macrophages. Macrophages were treated with the tacrolimus to assess gene expression in a time-dependent (1, 2, 4, 8, and 24 hr) and dose-dependent (concentrations [micrograms/liter] corresponding to the trough [15], peak [30], and 4x peak [120]) manner using reverse-transcriptase polymerase chain reactions. The gene expression levels of interest were normalized to GAPDH expression in each sample to provide semiquantitative reverse-transcriptase polymerase chain reaction results. Additional immunoblotting studies demonstrated protein expression of CD36, PPARγ, and ABCA1. Results. The gene expression of CD36, SR-BII, and lectin-like oxidized low-density lipoprotein receptor-1 were down-regulated, and ABCA1 was up-regulated. CD68, SR-AI, liver-X-receptor-α, and PPARγ were regulated in a dose-dependent manner. Protein expression of CD36 was down-regulated, and PPARγ and ABCA1 were relatively unchanged. Conclusions. Tacrolimus seems to regulate MSRs, nuclear hormone receptors, and ABCA1 in THP-1 macrophages. These results differ from previous findings with CsA and may provide insight into the mechanisms of posttransplant atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1281-1287
Number of pages7
JournalTransplantation
Volume77
Issue number8
DOIs
StatePublished - Apr 27 2004

All Science Journal Classification (ASJC) codes

  • Transplantation

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