Frontiers in genetics · 2026
Research of N-acetyl-L-cysteine on CD40-CD40L pathway in pulmonary fibrosis induced by silicon dioxide.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Shujuan, Wang Lili, Hu Kui, Han Jingyin, Gan Xiaoyu, Lou Yi, Li Guohui
Аннотация
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.
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.