Apoptotic cells trigger the ABCA1/STAT6 pathway leading to PPAR-γ expression and activation in macrophages

Myeong Joo Kim, Ye Ji Lee, Young So Yoon, Minsuk Kim, Ji Ha Choi, Hee Sun Kim, Jihee Lee Kang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The signal transducer and activator of transcription 6 (STAT6) transcription factor activates peroxisome proliferator-activated receptor gamma (PPAR-γ)-regulated gene expression in immune cells. We investigated proximal membrane signaling that was initiated in macrophages after exposure to apoptotic cells that led to enhanced PPAR-γ expression and activity, using specific siRNAs for ABCA1, STAT6, and PPAR-γ, or their antagonists. The interactions between mouse bone marrow-derived macrophages or RAW 264.7 cells and apoptotic Jurkat cells, but not viable cells, resulted in the induction of STAT6 phosphorylation as well as PPAR-γ expression and activation. Knockdown of ATP-binding cassette transporter A1 (ABCA1) after the transfection of macrophages with ABCA1-specific siRNAs reduced apoptotic cell-induced STAT6 phosphorylation as well as PPAR-γ mRNA and protein expression. ABCA1 knockdown also reduced apoptotic cell-induced liver X receptor α (LXR-α) mRNA and protein expression. Moreover, inhibition of STAT6 with specific siRNAs or the pharmacological inhibitor AS1517499AS reversed the induction of PPAR-γ, LXR-α, and ABCA1 by apoptotic Jurkat cells. PPAR-γ-specific siRNAs or the PPAR-γ antagonist GW9662 inhibited apoptotic cell-induced increases in LXR-α and ABCA1 mRNA and protein levels. Thus, these results indicate that apoptotic cells trigger the ABCA1/STAT6 pathway, leading to the activation of the PPAR-γ/LXR-α/ABCA1 pathway in macrophages.

Original languageEnglish
Pages (from-to)885-895
Number of pages11
JournalJournal of Leukocyte Biology
Volume103
Issue number5
DOIs
StatePublished - May 2018

Keywords

  • bone marrow-derived macrophages
  • mice
  • proximal membrane signaling
  • pulmonary fibrosis

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