Duggirala Vamsee K, Geary Kyla, Hasenmayer Donald, Daghigh Farzaneh
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine Philadelphia, PA, USA.
J Lipids. 2022 Aug 25;2022:3062274. doi: 10.1155/2022/3062274. eCollection 2022.
Airway remodeling (AR) increases disease severity, and morbidity of asthmatic patients by contributing to irreversible airflow obstruction and progressive declines in lung function. Arginase isoenzymes and the downstream enzymes ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) have been implicated in the hyperplastic and fibrotic changes of AR, respectively. Omega-3 polyunsaturated fatty acids (-3 PUFAs) and resolvin metabolites have anti-AR effects, but whether they are mediated through the arginase pathway is unclear. Our study intended to determine the effects of the -3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), resolvin D1 (RvD1), T1 cytokines, acetylsalicylic acid (ASA), cAMP, and dexamethasone (DEX) on the expression of arginase isoenzymes arginase 1 (ARG1) and arginase 2 (ARG2), ODC, and OAT in human lung fibroblasts (HLF) from normal (NHLF) and diseased (DHLF) asthmatic donors using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Our data showed that EPA and EPA+DHA downregulated ARG2 mRNA 2-fold in both types of HLF. DHA, RvD1, and DEX did not alter mRNA levels for any of the genes studied. EPA lowered the ARG2 protein levels in DHLF, but did not affect those levels in NHLF. ASA upregulated ARG2 mRNA 5-fold and 7-fold in NHLF and DHLF, respectively, T1 cytokines downregulated ARG2, ODC, and OAT mRNA in DHLF 10-fold, 2-fold, and 2.5-fold, respectively, and cAMP downregulated ARG2 mRNA 2-fold in DHLF. These results are the first to show a direct effect of -3 PUFAs on ARG2 mRNA levels and provide further evidence for a role of -3 PUFAs in AR.
气道重塑（AR）会导致哮喘患者出现不可逆的气流阻塞和肺功能逐渐下降，从而加重疾病的严重程度和发病率。精氨酸酶同工酶以及下游的鸟氨酸脱羧酶（ODC）和鸟氨酸转氨酶（OAT）分别与AR的增生性和纤维化改变有关。ω-3多不饱和脂肪酸（-3 PUFAs）和消退素代谢产物具有抗AR作用，但它们是否通过精氨酸酶途径介导尚不清楚。我们的研究旨在通过逆转录定量实时聚合酶链反应（RT-qPCR），确定-3 PUFAs二十碳五烯酸（EPA）、二十二碳六烯酸（DHA）、消退素D1（RvD1）、T1细胞因子、乙酰水杨酸（ASA）、环磷酸腺苷（cAMP）和地塞米松（DEX）对来自正常（NHLF）和患病（DHLF）哮喘供体的人肺成纤维细胞（HLF）中精氨酸酶同工酶精氨酸酶1（ARG1）和精氨酸酶2（ARG2）、ODC和OAT表达的影响。我们的数据表明，EPA和EPA+DHA在两种类型的HLF中均使ARG2 mRNA下调了2倍。DHA、RvD1和DEX对所研究的任何基因的mRNA水平均无影响。EPA降低了DHLF中ARG2蛋白水平，但对NHLF中的该水平没有影响。ASA在NHLF和DHLF中分别使ARG2 mRNA上调了5倍和7倍，T1细胞因子在DHLF中分别使ARG2、ODC和OAT mRNA下调了10倍、2倍和2.5倍，cAMP在DHLF中使ARG2 mRNA下调了2倍。这些结果首次表明-3 PUFAs对ARG2 mRNA水平有直接影响，并为-3 PUFAs在AR中的作用提供了进一步的证据。
