Department of Respiratory Medicine, Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
PLoS One. 2012;7(6):e38984. doi: 10.1371/journal.pone.0038984. Epub 2012 Jun 18.
Glutaredoxins (Grx) are redox enzymes that remove glutathione bound to protein thiols, know as S-glutathionylation (PSSG). PSSG is a reservoir of GSH and can affect the function of proteins. It inhibits the NF-κB pathway and LPS aspiration in Grx1 KO mice with decreased inflammatory cytokine levels. In this study we investigated whether absence of Grx1 similarly repressed cigarette smoke-induced inflammation in an exposure model in mice. Cigarette smoke exposure for four weeks decreased lung PSSG levels, but increased PSSG in lavaged cells and lavage fluid (BALF). Grx1 KO mice had increased levels of PSSG in lung tissue, BALF and BAL cells in response to smoke compared to wt mice. Importantly, levels of multiple inflammatory mediators in the BALF were decreased in Grx1 KO animals following cigarette smoke exposure compared to wt mice, as were levels of neutrophils, dendritic cells and lymphocytes. On the other hand, macrophage numbers were higher in Grx1 KO mice in response to smoke. Although cigarette smoke in vivo caused inverse effects in inflammatory and resident cells with respect to PSSG, primary macrophages and epithelial cells cultured from Grx1 KO mice both produced less KC compared to cells isolated from WT mice after smoke extract exposure. In this manuscript, we provide evidence that Grx1 has an important role in regulating cigarette smoke-induced lung inflammation which seems to diverge from its effects on total PSSG. Secondly, these data expose the differential effect of cigarette smoke on PSSG in inflammatory versus resident lung cells.
谷氧还蛋白（Grx）是一种可以还原结合在蛋白质巯基上的谷胱甘肽的氧化还原酶，这种还原反应被称为 S-谷胱甘肽化（PSSG）。PSSG 是 GSH 的储备库，能够影响蛋白质的功能。它能够抑制 NF-κB 通路和 Grx1 KO 小鼠中的 LPS 摄取，同时降低促炎细胞因子的水平。在本研究中，我们调查了 Grx1 的缺失是否同样能够抑制暴露于香烟烟雾中的小鼠模型中的炎症反应。四周的香烟烟雾暴露降低了肺部的 PSSG 水平，但增加了灌洗液细胞和灌洗液中的 PSSG。与野生型小鼠相比，Grx1 KO 小鼠在暴露于烟雾后肺部组织、灌洗液和灌洗液细胞中的 PSSG 水平更高。重要的是，与野生型小鼠相比，Grx1 KO 动物在暴露于香烟烟雾后，BALF 中的多种炎症介质水平下降，中性粒细胞、树突状细胞和淋巴细胞的水平也下降。另一方面，Grx1 KO 小鼠中的巨噬细胞数量在暴露于烟雾后增加。尽管体内的香烟烟雾在 PSSG 方面对炎症细胞和固有细胞产生了相反的影响，但与来自 WT 小鼠的细胞相比，来自 Grx1 KO 小鼠的原代巨噬细胞和上皮细胞在暴露于烟雾提取物后产生的 KC 都较少。在本手稿中，我们提供了证据表明 Grx1 在调节香烟烟雾引起的肺炎症中具有重要作用，这似乎与其对总 PSSG 的影响不同。其次，这些数据揭示了香烟烟雾对炎症细胞和固有肺细胞中 PSSG 的不同影响。
