{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:34:17Z","timestamp":1777358057886,"version":"3.51.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute lung inflammation has recently gained increasing attention due to the high acute respiratory distress syndrome complications with subsequent fibrosis during the COVID-19 pandemic. Our group identified that the antifibrotic effect of the antidepressant fluvoxamine (FLU) in various organs is meditated via sigma-1 receptor (S1R) agonism. Since the actions of FLU on the inflammatory components have not been elucidated, this study investigated its effects in a mouse model of interstitial pneumonitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Pneumonitis was induced in wild-type (WT) and S1R knockout (\n                      <jats:italic>S1r<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      ) mice by intratracheal administration of lipopolysaccharide: 0.5\u00a0mg\/kg LPS. Treatment groups were randomized into 1) phosphate-buffered saline (PBS) +vehicle, 2) LPS + vehicle, 3) LPS + FLU (\n                      <jats:italic>i.p.<\/jats:italic>\n                      20\u00a0mg x bwkg\n                      <jats:sup>-1<\/jats:sup>\n                      ) or 4) LPS + dexamethasone (\n                      <jats:italic>i.p.<\/jats:italic>\n                      5\u00a0mg x bwkg\n                      <jats:sup>-1<\/jats:sup>\n                      ) groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LPS reduced tidal volume, minute ventilation, peak expiratory, inspiratory and mid-tidal expiratory flows. Similarly to the reference compound dexamethasone FLU counteracted all effects in WT, but not in\n                      <jats:italic>S1r<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice. Furthermore, FLU alleviated LPS-induced macrophage infiltration in both genotypes, but had no effect on lung edema or neutrophil accumulation. FLU downregulated inflammatory cytokines IL-1, IL-6, TNF-\u03b1, and MCP-1 in WT mice\n                      <jats:italic>,<\/jats:italic>\n                      similarly to dexamethasone, but not in\n                      <jats:italic>S1r<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, FLU mitigates LPS-induced pulmonary inflammation and functional deterioration primarily via S1R signaling, highlighting a receptor-specific mechanism underlying its protective effects. Thus, targeting S1R may be an effective and safe alternative to other therapeutic approaches, including glucocorticoids to treat inflammatory lung injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1818198","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:36:43Z","timestamp":1777354603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The sigma-1 receptor agonist fluvoxamine alleviates endotoxin-induced acute lung injury in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Emese","family":"Ritter","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, University of P\u00e9cs, Medical School","place":["P\u00e9cs, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kata","family":"Csek\u0151","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, University of P\u00e9cs, Medical School","place":["P\u00e9cs, Hungary"]},{"name":"National Laboratory for Drug Research and Development","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1d\u00e1m","family":"Hossz\u00fa","sequence":"additional","affiliation":[{"name":"MTA-SE Lend\u00fclet \u201cMomentum\u201d Diabetes Research Group","place":["Budapest, Hungary"]},{"name":"Pediatric Center, Semmelweis University","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1kos R.","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"MTA-SE Lend\u00fclet \u201cMomentum\u201d Diabetes Research Group","place":["Budapest, Hungary"]},{"name":"Pediatric Center, Semmelweis University","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00f3ra","family":"Hargitai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, Faculty of Medicine","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Kereskai","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of P\u00e9cs, Medical School","place":["P\u00e9cs, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Fekete","sequence":"additional","affiliation":[{"name":"MTA-SE Lend\u00fclet \u201cMomentum\u201d Diabetes Research Group","place":["Budapest, Hungary"]},{"name":"Pediatric Center, Semmelweis University","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, University of P\u00e9cs, Medical School","place":["P\u00e9cs, Hungary"]},{"name":"National Laboratory for Drug Research and Development","place":["Budapest, Hungary"]},{"name":"HUN-REN-PTE Chronic Pain Research Group","place":["P\u00e9cs, Hungary"]},{"name":"PharmInVivo Hungary Ltd.","place":["P\u00e9cs, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"705575","DOI":"10.3389\/fphys.2021.705575","article-title":"Sigmar1\u2019s molecular, cellular, and biological functions in regulating cellular pathophysiology","volume":"12","author":"Aishwarya","year":"2021","journal-title":"Front. 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