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Gasdermin D regulates soluble fms-like tyrosine kinase 1 release in macrophages.
Tanaka, Hazuki; Ozawa, Ren; Henmi, Yuka; Hosoda, Manabu; Karasawa, Tadayoshi; Takahashi, Masafumi; Takahashi, Hironori; Iwata, Hisataka; Kuwayama, Takehito; Shirasuna, Koumei.
Afiliación
  • Tanaka H; Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Japan.
  • Ozawa R; Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Japan.
  • Henmi Y; Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Japan.
  • Hosoda M; Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Japan.
  • Karasawa T; Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Japan.
  • Takahashi M; Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Japan.
  • Takahashi H; Department of Obstetrics and Gynecology, Jichi Medical University, Japan.
  • Iwata H; Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Japan.
  • Kuwayama T; Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Japan.
  • Shirasuna K; Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Japan. Electronic address: ks205312@nodai.ac.jp.
Reprod Biol ; 24(1): 100857, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38295720
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)- 1ß, but did not induce cell lytic death. IL-1ß 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-1ß and sFLT1 secretion from THP-1 cells. Treatment with CA074-ME (a cathepsin B inhibitor) also reduced the secretion of both sFLT1 and IL-1ß 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR Límite: Humans Idioma: En Revista: Reprod Biol Asunto de la revista: MEDICINA REPRODUTIVA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Polonia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR Límite: Humans Idioma: En Revista: Reprod Biol Asunto de la revista: MEDICINA REPRODUTIVA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Polonia