ArticleFrontiers in genetics2026
Research of N-acetyl-L-cysteine on CD40-CD40L pathway in pulmonary fibrosis induced by silicon dioxide.
Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: To investigate the effect of N-acetyl-L-cysteine (NAC) on the CD40-CD40L signaling axis during the development of pulmonary fibrosis in silicosis. Methods: 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-γ (IFN-γ), 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 α-smooth muscle actin (α-SMA) expression by Western blotting. Results: 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-γ, 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 α-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 α-SMA fluorescence versus the silicosis group, whereas BALF from intervention-1 and intervention-2 significantly reduced HFL-1 α-SMA and Collagen I expression, with intervention-2 yielding the largest effect. Discussion: NAC downregulates T-cell surface CD40L expression and disrupts CD40-CD40L interactions, attenuating production of multiple proinflammatory cytokines, reducing collagen synthesis and deposition, and thereby delaying the progression of interstitial pulmonary fibrosis in silicosis.
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