| First Author | Kim MJ | Year | 2018 |
| Journal | J Leukoc Biol | Volume | 103 |
| Issue | 5 | Pages | 885-895 |
| PubMed ID | 29603355 | Mgi Jnum | J:261796 |
| Mgi Id | MGI:6155309 | Doi | 10.1002/JLB.2A0817-341RR |
| Citation | Kim MJ, et al. (2018) Apoptotic cells trigger the ABCA1/STAT6 pathway leading to PPAR-gamma expression and activation in macrophages. J Leukoc Biol 103(5):885-895 |
| abstractText | The signal transducer and activator of transcription 6 (STAT6) transcription factor activates peroxisome proliferator-activated receptor gamma (PPAR-gamma)-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-gamma expression and activity, using specific siRNAs for ABCA1, STAT6, and PPAR-gamma, 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-gamma 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-gamma mRNA and protein expression. ABCA1 knockdown also reduced apoptotic cell-induced liver X receptor alpha (LXR-alpha) mRNA and protein expression. Moreover, inhibition of STAT6 with specific siRNAs or the pharmacological inhibitor AS1517499AS reversed the induction of PPAR-gamma, LXR-alpha, and ABCA1 by apoptotic Jurkat cells. PPAR-gamma-specific siRNAs or the PPAR-gamma antagonist GW9662 inhibited apoptotic cell-induced increases in LXR-alpha 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-gamma/LXR-alpha/ABCA1 pathway in macrophages. |
