論文 - 詳細
| RRC ID | 64119 |
|---|---|
| 著者 | Nurrahmah QI, Madhyastha R, Madhyastha H, Purbasari B, Maruyama M, Nakajima Y. |
| タイトル | Retinoic acid abrogates LPS-induced inflammatory response via negative regulation of NF-kappa B/miR-21 signaling. |
| ジャーナル | Immunopharmacol Immunotoxicol |
| Abstract |
CONTEXT:Macrophages are essential components of the immune system, with significant roles in inflammation modulation. They can be activated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes, depending on their micro-environment. Molecular factors that modulate macrophage polarization are hot targets for therapeutic strategies to counter chronic inflammatory pathological conditions. OBJECTIVE:The current study aimed to elucidate the molecular mechanisms by which Retinoic acid (RA), a potent immunomodulator, suppresses LPS-induced inflammatory response in macrophages. MATERIALS AND METHODS:RAW 264.7 macrophages were treated with RA and/or LPS, and analyzed for inflammatory genes and miR-21 by PCR. The roles of miR-21 and NF-ĸB signaling pathway were also assessed by knock-down experiments, immunofluorescence, and ChIP assays. RESULTS:Pretreatment with RA quenched the LPS-induced inflammatory responses, including phagocytosis, ROS generation, and NO production. RA shifted the polarization away from the M1 state by negative regulation of IKKα/β, p65, and miR-21. RA hindered the phosphorylation of IKKα/β, translocation of p65 into the nucleus, and the subsequent upregulation of miR-21. Knock-in and knock-down experiments showed that miR-21 is central for the polarization shift toward the pro-inflammatory M1 state. CONCLUSION:miR-21 is involved in the LPS-induced pro-inflammatory profile of macrophages and that RA negatively regulates the inflammatory response by targeting NF-ĸB/miR-21 signaling. Our data exposes RA's potential as a pharmacological agent to manipulate miR-21 and counteract hyper-inflammatory response. |
| 巻・号 | 43(3) |
| ページ | 299-308 |
| 公開日 | 2021-6-1 |
| DOI | 10.1080/08923973.2021.1902348 |
| PMID | 33757404 |
| MeSH | Animals Inflammation / chemically induced Inflammation / metabolism Lipopolysaccharides / toxicity* Macrophages / metabolism* Mice MicroRNAs / metabolism* NF-kappa B / metabolism* RAW 264.7 Cells Signal Transduction / drug effects* Tretinoin / pharmacology* |
| IF | 2.352 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |