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Both cytotoxic NK cells and TH17 cells are heavily influenced via IL-1\u03b2 signaling. Caspase 1 activity leads to the release of the inflammatory cytokine IL-1\u03b2, which is increased in women with PE. Therefore, we tested the hypothesis that the inhibition of Caspase 1 with VX-765 in rats with reduced uterine perfusion pressure (RUPP) will attenuate PE pathophysiology. On gestation day (GD) 14, timed pregnant Sprague\u2013Dawley rats underwent the RUPP or Sham procedure and were separated into groups that received either vehicle or VX-765 (50 mg\/kg\/day i.p.). On GD19, MAP was measured via carotid catheter and blood and tissues were collected. Bio-Plex and flow cytometry analysis were performed on placental tissues. Placental IL-1\u03b2 was increased in the RUPP rats vs. the Sham rats and treatment with VX-765 reduced IL-1\u03b2 in the RUPP rats. Caspase 1 inhibition reduced placental cNKs and TH17s in RUPP rats compared to vehicle-treated RUPP rats. Increased MAP was observed in RUPP rats compared with Sham rats and was reduced in RUPP + VX-765 rats. Placental reactive oxygen species (ROS) were elevated in RUPP rats compared to Sham rats. VX-765 administration reduced ROS in treated RUPP rats. Caspase 1 inhibition increased the number of live pups, yet had no effect on fetal weight or placental efficiency in the treated groups. In conclusion, Caspase 1 inhibition reduces placental IL-1\u03b2, inflammatory TH17 and cNK populations, and reduces MAP in RUPP rats. These data suggest that Caspase 1 is a key contributor to PE pathophysiology. This warrants further investigation of Caspase 1 as a potential therapeutic target to improve maternal outcomes in PE.<\/jats:p>","DOI":"10.3390\/ijms25020863","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:39:57Z","timestamp":1704879597000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of Caspase 1 Reduces Blood Pressure, Cytotoxic NK Cells, and Inflammatory T-Helper 17 Cells in Placental Ischemic Rats"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2607-051X","authenticated-orcid":false,"given":"Corbin A.","family":"Shields","sequence":"first","affiliation":[{"name":"Department of Pharmacolocy and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geilda A.","family":"Tardo","sequence":"additional","affiliation":[{"name":"Department of Pharmacolocy and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacolocy and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Peacock","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Robbins","sequence":"additional","affiliation":[{"name":"Department of Pharmacolocy and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Glenn","sequence":"additional","affiliation":[{"name":"Department of Pharmacolocy and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Pharmacolocy and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pharmacolocy and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6730-6499","authenticated-orcid":false,"given":"Denise C.","family":"Cornelius","sequence":"additional","affiliation":[{"name":"Department of Pharmacolocy and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2050312119843700","DOI":"10.1177\/2050312119843700","article-title":"Hypertension in pregnancy: Pathophysiology and treatment","volume":"7","author":"Braunthal","year":"2019","journal-title":"SAGE Open Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mu, T.S., Duran-Stanton, A., Stone, E.A., Zarzabal, L.A., and Loewendorf, A. 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