| RRC ID |
89871
|
| Author |
Lyu J, Fukunaga K, He Z, Imachi H, Kobayashi T, Saheki T, Yoshimura T, Harada E, Izumi K, Jiang W, Zhang H, Rathana L, Iwama H, Guo J, Murao K.
|
| Title |
Interleukin-1β decreases hepatic ATP-binding cassette subfamily A member 1 expression through p38 mitogen-activated protein kinase signaling and an H-89-sensitive pathway.
|
| Journal |
Endocr J
|
| Abstract |
Steatotic liver disease is a common metabolic disorder, and interleukin-1β (IL-1β) contributes to hepatic inflammation and lipid accumulation. ATP-binding cassette subfamily A member 1 (ABCA1) regulates cholesterol efflux and lipid homeostasis. This study examined whether IL-1β suppresses hepatic ABCA1 expression and explored the underlying signaling and transcriptional mechanisms. Primary mouse hepatocytes and HepG2 cells were treated with IL-1β. ABCA1 expression was assessed by Western blotting and RT-qPCR, and ABCA1 promoter activity was examined using luciferase reporter assays with inhibitors targeting phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (p38 MAPK), or an H-89-sensitive pathway. Prolactin regulatory element-binding protein (PREB) involvement was evaluated by nuclear protein analysis, PREB-binding-site mutation, and siRNA-mediated knockdown. Lipid accumulation was assessed by intracellular cholesterol measurement and Oil Red O staining. IL-1β decreased ABCA1 protein and mRNA expression in a dose- and time-dependent manner and suppressed ABCA1 promoter activity. Inhibition of p38 MAPK or treatment with H-89 attenuated IL-1β-induced suppression of promoter activity and endogenous ABCA1 expression. Representative immunoblotting showed that IL-1β enhanced p38 MAPK phosphorylation, whereas SB203580 attenuated this response. IL-1β reduced nuclear PREB expression, and p38 MAPK inhibition restored nuclear PREB expression. Mutation of the PREB-binding site or PREB knockdown abolished IL-1β-mediated suppression of ABCA1 expression. IL-1β also increased intracellular cholesterol content and Oil Red O-positive lipid accumulation. These findings suggest that IL-1β suppresses hepatic ABCA1 expression through p38 MAPK signaling and an H-89-sensitive pathway, at least partly involving PREB-associated transcriptional regulation, and that this suppression is associated with hepatocellular lipid accumulation.
|
| Published |
2026-8-25
|
| DOI |
10.1507/endocrj.EJ26-0223
|
| PMID |
42649050
|
| Resource |
| Human and Animal Cells |
Hep G2(RCB1648) |
