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Apoptotic cells trigger the ABCA1/STAT6 pathway leading to PPAR- expression and activation in macrophages
- Apoptotic cells trigger the ABCA1/STAT6 pathway leading to PPAR- expression and activation in macrophages
- Kim, Myeong-Joo; Lee, Ye-Ji; Yoon, Young-So; Kim, Minsuk; Choi, Ji Ha; Kim, Hee-Sun; Kang, Jihee Lee
- Ewha Authors
- 이지희; 김희선; 최지하; 김민석
- SCOPUS Author ID
- 이지희; 김희선; 최지하; 김민석
- Issue Date
- Journal Title
- JOURNAL OF LEUKOCYTE BIOLOGY
- JOURNAL OF LEUKOCYTE BIOLOGY vol. 103, no. 5, pp. 885 - 895
- bone marrow-derived macrophages; mice; proximal membrane signaling; pulmonary fibrosis
- SCIE; SCOPUS
- Document Type
- The signal transducer and activator of transcription 6 (STAT6) transcription factor activates peroxisome proliferator-activated receptor gamma (PPAR-)-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- expression and activity, using specific siRNAs for ABCA1, STAT6, and PPAR-, 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- 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- mRNA and protein expression. ABCA1 knockdown also reduced apoptotic cell-induced liver X receptor (LXR-) mRNA and protein expression. Moreover, inhibition of STAT6 with specific siRNAs or the pharmacological inhibitor AS1517499AS reversed the induction of PPAR-, LXR-, and ABCA1 by apoptotic Jurkat cells. PPAR--specific siRNAs or the PPAR- antagonist GW9662 inhibited apoptotic cell-induced increases in LXR- 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-/LXR-/ABCA1 pathway in macrophages. The ABCA1-STAT6 pathway initiated by apoptotic cells is reinforced via a PPAR pathway.
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