{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:33:01Z","timestamp":1792153981083,"version":"4.4.0"},"reference-count":110,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Italian University and Research","award":["FUR 2018"],"award-info":[{"award-number":["FUR 2018"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie Grant Agreement","award":["754345"],"award-info":[{"award-number":["754345"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Available evidence shows that human cortical neurons\u2019 and astrocytes\u2019 calcium-sensing receptors (CaSRs) bind Amyloid-beta (A\u03b2) oligomers triggering the overproduction\/oversecretion of several Alzheimer\u2019s disease (AD) neurotoxins\u2014effects calcilytics suppress. We asked whether A\u03b2\u2022CaSR signaling might also play a direct pro-neuroinflammatory role in AD. Cortical nontumorigenic adult human astrocytes (NAHAs) in vitro were untreated (controls) or treated with A\u03b225\u201335 \u00b1 NPS 2143 (a calcilytic) and any proinflammatory agent in their protein lysates and growth media assayed via antibody arrays, enzyme-linked immunosorbent assays (ELISAs), and immunoblots. Results show A\u03b2\u2022CaSR signaling upregulated the synthesis and release\/shedding of proinflammatory interleukin (IL)-6, intercellular adhesion molecule-1 (ICAM-1) (holoprotein and soluble [s] fragment), Regulated upon Activation, normal T cell Expressed and presumably Secreted (RANTES), and monocyte chemotactic protein (MCP)-2. Adding NPS 2143 (i) totally suppressed IL-6\u2032s oversecretion while remarkably reducing the other agents\u2019 over-release; and (ii) more effectively than A\u03b2 alone increased over controls the four agents\u2019 distinctive intracellular accumulation. Conversely, NPS 2143 did not alter A\u03b2-induced surges in IL-1\u03b2, IL-3, IL-8, and IL-16 secretion, consequently revealing their A\u03b2\u2022CaSR signaling-independence. Finally, A\u03b225\u201335 \u00b1 NPS 2143 treatments left unchanged MCP-1\u2032s and TIMP-2\u2032s basal expression. Thus, NAHAs A\u03b2\u2022CaSR signaling drove four proinflammatory agents\u2019 over-release that NPS 2143 curtailed. Therefore, calcilytics would also abate NAHAs\u2019 A\u03b2\u2022CaSR signaling direct impact on AD\u2019s neuroinflammation.<\/jats:p>","DOI":"10.3390\/cells9061386","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T04:12:09Z","timestamp":1591157529000},"page":"1386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["CaSR Antagonist (Calcilytic) NPS 2143 Hinders the Release of Neuroinflammatory IL-6, Soluble ICAM-1, RANTES, and MCP-2 from A\u03b2-Exposed Human Cortical Astrocytes"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6974-7685","authenticated-orcid":false,"given":"Anna","family":"Chiarini","sequence":"first","affiliation":[{"name":"Human Histology and Embryology Section, Department of Surgery, Dentistry, Pediatrics and Gynecology, Medical School, University of Verona, Veneto, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-6143","authenticated-orcid":false,"given":"Ubaldo","family":"Armato","sequence":"additional","affiliation":[{"name":"Human Histology and Embryology Section, Department of Surgery, Dentistry, Pediatrics and Gynecology, Medical School, University of Verona, Veneto, 37134 Verona, Italy"},{"name":"Burns Department, Shenzhen Second People\u2019s Hospital, University of Shenzhen, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Hu","sequence":"additional","affiliation":[{"name":"Human Histology and Embryology Section, Department of Surgery, Dentistry, Pediatrics and Gynecology, Medical School, University of Verona, Veneto, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Dal Pr\u00e0","sequence":"additional","affiliation":[{"name":"Human Histology and Embryology Section, Department of Surgery, Dentistry, Pediatrics and Gynecology, Medical School, University of Verona, Veneto, 37134 Verona, Italy"},{"name":"Burns Department, Shenzhen Second People\u2019s Hospital, University of Shenzhen, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"ref_1","unstructured":"Prince, M.J., Wimo, A., Guerchet, M.M., Ali, G.C., Wu, Y.-T., and Prina, M. 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