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Gasdermin D regulates soluble fms-like tyrosine kinase 1 release in macrophages.
- Source :
-
Reproductive biology [Reprod Biol] 2024 Mar; Vol. 24 (1), pp. 100857. Date of Electronic Publication: 2024 Jan 30. - Publication Year :
- 2024
-
Abstract
- Preeclampsia (PE) is a serious complication, and soluble fms-like tyrosine kinase (sFLT1) released from the placenta is one of the causes of PE pathology. Trophoblasts are the primary source of sFLT1; however, monocytes/macrophages exist enough in the placenta can also secrete sFLT1. Sterile inflammatory responses, especially NLRP3 inflammasome and its downstream gasdermin D (GSDMD)-regulated pyroptosis, may be involved in the development of PE pathology. In this study, we investigated whether human monocyte/macrophage cell line THP-1 cells secrete sFLT1 depending on the NLRP3 inflammasome and GSDMD. To differentiate THP-1 monocytes into macrophages, treatment with phorbol 12-myristate 13-acetate (PMA) induced sFLT1 with interleukin (IL)- 1β, but did not induce cell lytic death. IL-1β secretion induced by PMA inhibited by deletion of NLRP3 and inhibitors of NLRP3 and caspase-1, but deletion of NLRP3 and these inhibitors did not affect sFLT1 secretion in THP-1 cells. Both gene deletion and inhibition of GSDMD dramatically decreased IL-1β and sFLT1 secretion from THP-1 cells. Treatment with CA074-ME (a cathepsin B inhibitor) also reduced the secretion of both sFLT1 and IL-1β in THP-1 cells. In conclusion, THP-1 macrophages release sFLT1 in a GSDMD-dependent manner, but not in the NLRP3 inflammasome-dependent manner, and this sFLT1 release may be associated with the non-lytic role of GSDMD. In addition, sFLT1 levels induced by PMA are associated with lysosomal cathepsin B in THP-1 macrophages. We suggest that sFLT1 synthesis regulated by GSDMD are involved in the pathology of PE.<br />Competing Interests: Conflicts of Interest The authors have no conflicts of interest directly relevant to the content of this article.<br /> (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Vascular Endothelial Growth Factor Receptor-1 genetics
Vascular Endothelial Growth Factor Receptor-1 metabolism
Cathepsin B metabolism
Gasdermins
Macrophages metabolism
NLR Family, Pyrin Domain-Containing 3 Protein genetics
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Inflammasomes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2300-732X
- Volume :
- 24
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Reproductive biology
- Publication Type :
- Academic Journal
- Accession number :
- 38295720
- Full Text :
- https://doi.org/10.1016/j.repbio.2024.100857