{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:20:21Z","timestamp":1790796021233,"version":"4.1.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Regulation of inflammation and re-epithelialization are critical for efficient wound healing. This study explores the role of human \u03b11-antitrypsin (hAAT), an immunomodulatory protein, in modulating inflammation and promoting re-epithelialization across various epithelial cell types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In-vitro<\/jats:italic>\n                      , epithelial gap closure and migration assays were performed using two human epithelial cell lines\u2014HaCaT and A549 cells with and without mitomycin C treatment. These cell lines were also used in an\n                      <jats:italic>in-vitro<\/jats:italic>\n                      gel-directed epithelial migration assay. Cells were treated with hAAT, and the gap area was measured using image analysis. Gene expression of inflammatory markers (IL-1\u03b2, IL-6, and TNF\u03b1) and adhesion molecules (desmoglein-1, plectin, and integrin \u03b16\u03b24) were analyzed using qPCR.\n                      <jats:italic>In-vivo<\/jats:italic>\n                      , corneal abrasions were induced in C57BL\/6 mice using an Ophthalmic Burr. Mice received topical hAAT treatment immediately after injury and every 6 hours thereafter. Wound closure was assessed by applying the standard ophthalmic staining technique, fluorescein, and image analysis. Inflammatory markers and adhesion molecule expression were evaluated using qPCR and immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In-vitro<\/jats:italic>\n                      , hAAT accelerated epithelial gap closure and increased migration distance, independent of cell proliferation. hAAT-treated cells also exhibited earlier peak expressions of IL-1\u03b2 and IL-6.\n                      <jats:italic>In-vivo<\/jats:italic>\n                      , hAAT treatment accelerated corneal wound closure and resulted in a preference for IL-1Ra over IL-1\u03b2 expression. hAAT also enhanced the expression of desmoglein-1, plectin, and integrin \u03b16\u03b24, both\n                      <jats:italic>in-vitro<\/jats:italic>\n                      and\n                      <jats:italic>in-vivo<\/jats:italic>\n                      , and increased desmoglein-1 expression in the epithelial migration zone of mouse cornea.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>hAAT enhances re-epithelialization by modulating inflammation, promoting epithelial cell migration, and regulating expression of adhesion molecules.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1586039","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:10:33Z","timestamp":1748563833000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Alpha-1 antitrypsin promotes re-epithelialization by regulating inflammation and 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