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Apoptotic cells trigger the ABCA1/STAT6 pathway leading to PPAR‐γ expression and activation in macrophages
Author(s) -
Kim MyeongJoo,
Lee YeJi,
Yoon YoungSo,
Kim Minsuk,
Choi Ji Ha,
Kim HeeSun,
Kang Jihee Lee
Publication year - 2018
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.2a0817-341rr
Subject(s) - jurkat cells , small interfering rna , gene knockdown , biology , microbiology and biotechnology , abca1 , transfection , peroxisome proliferator activated receptor , apoptosis , cancer research , cell culture , receptor , immunology , biochemistry , t cell , immune system , genetics , transporter , gene
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.