| Title: | Methylprednisolone pulse-enhanced neutrophil extracellular trap formation in mice with imiquimod-induced lupus-like disease, resulting in ischaemia of the femoral head cartilage |
| Authors: | Ogawa, Hodaka Browse this author |
| Yokota, Shunichi Browse this author |
| Hosoi, Yumeka Browse this author |
| Shindo, Ayano Browse this author |
| Ogawa, Naho Browse this author |
| Yamamura, Ryodai Browse this author →KAKEN DB |
| Shimizu, Tomohiro Browse this author →KAKEN DB |
| Nakade, Issei Browse this author |
| Arai, Suishin Browse this author |
| Taniguchi, Mai Browse this author |
| Nishibata, Yuka Browse this author |
| Masuda, Sakiko Browse this author →KAKEN DB |
| Nakazawa, Daigo Browse this author →KAKEN DB |
| Tomaru, Utano Browse this author →KAKEN DB |
| Iwasaki, Norimasa Browse this author →KAKEN DB |
| Ishizu, Akihiro Browse this author →KAKEN DB |
| Issue Date: | 28-Dec-2023 |
| Journal Title: | Lupus Science & Medicine |
| Volume: | 10 |
| Issue: | 2 |
| Start Page: | e001042 |
| Publisher DOI: | 10.1136/lupus-2023-001042 |
| PMID: | 38154828 |
| Abstract: | Objectives: Methylprednisolone (mPSL) pulse therapy is an essential option for patients with active systemic lupus erythematosus, but there is a risk of adverse events related to microcirculation disorders, including idiopathic osteonecrosis of the femoral head (ONFH). Recent studies have revealed that excessive neutrophil extracellular traps (NETs) are involved in microcirculation disorders. This study aimed to demonstrate that mPSL pulse could induce NETs in lupus mice and identify the factors contributing to this induction. Methods: Six mice with imiquimod (IMQ)-induced lupus-like disease and six normal mice were intraperitoneally injected with mPSL on days 39 to 41, and five mice with IMQ-induced lupus-like disease and six normal mice were injected with phosphate-buffered saline. Pathological examinations were conducted to evaluate the ischaemic state of the femoral head and tissue infiltration of NET-forming neutrophils. Proteome analysis was performed to extract plasma proteins specifically elevated in mPSL-administered mice with IMQ-induced lupus-like disease, and their effects on NET formation were assessed in vitro. Results: Mice with IMQ-induced lupus-like disease that received mPSL pulse demonstrated ischaemia of the femoral head cartilage with tissue infiltration of NET-forming neutrophils. Proteome analysis suggested that prenylcysteine oxidase 1 (PCYOX1) played a role in this phenomenon. The reaction of PCYOX1-containing very low-density lipoproteins (VLDL) with its substrate farnesylcysteine (FC) induced NETs in vitro. The combined addition of IMQ and mPSL synergistically enhanced VLDL-plus-FC-induced NET formation. Conclusion: PCYOX1 and related factors are worthy of attention to understand the underlying mechanisms and create novel therapeutic strategies for mPSL-mediated microcirculation disorders, including ONFH. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/91026 |
| Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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