{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:51:40Z","timestamp":1781736700437,"version":"3.54.5"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>To investigate the effect of N-acetyl-L-cysteine (NAC) on the CD40\u2013CD40L signaling axis during the development of pulmonary fibrosis in silicosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventy-five patients treated in our department between January 2018 and June 2023 were enrolled and allocated to five groups (n = 15 each): healthy control, silicosis, routine treatment, intervention-1, and intervention-2. Bronchoalveolar lavage fluid (BALF) was collected from all subjects. CD40L expression on T lymphocyte surfaces was measured by flow cytometry. BALF concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-\u03b3 (IFN-\u03b3), and monocyte chemoattractant protein-1 (MCP-1) were quantified by ELISA. BALF samples from each group were co-cultured with the human fetal lung fibroblast cell line HFL-1; Collagen I expression was assessed by immunocytochemistry and \u03b1-smooth muscle actin (\u03b1-SMA) expression by Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>T cells isolated from BALF of silicosis patients exhibited significantly higher surface CD40L expression than those from healthy controls. Both intervention groups showed marked reductions in T-cell CD40L expression compared with the untreated silicosis group, with the greatest decrease in intervention-2. BALF levels of IL-6, IL-8, IFN-\u03b3, and MCP-1 were significantly elevated in silicosis patients versus controls. Compared with the silicosis group, the routine treatment, intervention-1, and intervention-2 groups demonstrated progressive reductions in these cytokines, most pronounced in intervention-2. HFL-1 cells cultured with silicosis BALF displayed significantly increased \u03b1-SMA and Collagen I expression relative to cells exposed to control BALF. BALF from the routine treatment group produced no significant change in HFL-1 \u03b1-SMA fluorescence versus the silicosis group, whereas BALF from intervention-1 and intervention-2 significantly reduced HFL-1 \u03b1-SMA and Collagen I expression, with intervention-2 yielding the largest effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>NAC downregulates T-cell surface CD40L expression and disrupts CD40\u2013CD40L interactions, attenuating production of multiple proinflammatory cytokines, reducing collagen synthesis and deposition, and thereby delaying the progression of interstitial pulmonary fibrosis in silicosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1845040","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:10:25Z","timestamp":1781734225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Research of N-acetyl-L-cysteine on CD40\u2013CD40L pathway in pulmonary fibrosis induced by silicon dioxide"],"prefix":"10.3389","volume":"17","author":[{"given":"Shujuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Occupational Medicine, Hangzhou Red Cross Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Hangzhou Red Cross Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Hangzhou Red Cross Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Hangzhou Red Cross Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Hangzhou Red Cross Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Hangzhou Red Cross Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Hangzhou Red Cross Hospital","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"155239","DOI":"10.1016\/j.cyto.2020.155239","article-title":"The effects of N-Acetylcysteine on serum level of inflammatory biomarkers in adults. 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