Czarzasta J, Meller K, Andronowska A, Jana B
Division of Reproductive Biology, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Olsztyn, Poland.
Reprod Domest Anim. 2018 Feb;53(1):101-109. doi: 10.1111/rda.13077. Epub 2017 Sep 11.
Uterine inflammatory response is mediated by inflammatory mediators including eicosanoids and cytokines produced by immune and endometrial cells. Interactions between lipopolysaccharide (LPS) and cytokines, and leukotrienes (LTs) in endothelium, important for the host defence during the inflammation, are unknown. We studied the effect of LPS, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4 and IL-10 on 5-lipooxygenase (5-LO), LTA hydrolase (LTAH) and LTC synthase (LTCS) mRNA and protein expression, LTB and LTC release from porcine endometrial endothelial cells, and cell viability. For 24 hr, cells were exposed to LPS (10 or 100 ng/ml of medium) and cytokines (each 1 or 10 ng/ml). 5-LO mRNA/protein expression augmented after incubation with larger doses of LPS, TNF-α, IL-4 and IL-10 and smaller dose of IL-1β. Larger dose of TNF-α, smaller doses of LPS and IL-1β and both doses of IL-10 increased LTAH mRNA/protein expression. LTAH protein content was up-regulated by larger dose of LPS, but it was reduced in response to both doses of IL-4. LTCS mRNA expression was elevated by larger doses of LPS, IL-4 and IL-10 or both doses of TNF-α and IL-1β. LTCS protein level increased after treatment with both doses of IL-1β, IL-4 and IL-10, smaller dose of LPS and larger dose of TNF-α. Both doses of LPS and larger doses of TNF-α and IL-10 increased LTB release. LPS, IL-1β and IL-10 at smaller doses, or TNF-α and IL-4 at larger doses stimulated LTC release. Smaller doses of TNF-α and IL-1β or both doses of IL-4 enhanced the cell viability. This work provides new insight on the participation of LPS, TNF-α, IL-1β, IL-4 and IL-10 in LTB and LTC production/release from porcine endometrial endothelial cells, and the effect of above factors on these cells viability. The used cellular model gives the possibility to further establish the interactions between inflammatory mediators.
子宫炎症反应由免疫细胞和子宫内膜细胞产生的包括类花生酸和细胞因子在内的炎症介质介导。脂多糖（LPS）与细胞因子以及内皮细胞中的白三烯（LTs）之间的相互作用在炎症期间对宿主防御很重要，但目前尚不清楚。我们研究了LPS、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-4和IL-10对猪子宫内膜内皮细胞中5-脂氧合酶（5-LO）、LTA水解酶（LTAH）和LTC合酶（LTCS）mRNA和蛋白表达、LTB和LTC释放以及细胞活力的影响。细胞暴露于LPS（10或100 ng/ml培养基）和细胞因子（均为1或10 ng/ml）24小时。与较大剂量的LPS、TNF-α、IL-4和IL-10以及较小剂量的IL-1β孵育后，5-LO mRNA/蛋白表达增加。较大剂量的TNF-α、较小剂量的LPS和IL-1β以及两种剂量的IL-10均可增加LTAH mRNA/蛋白表达。较大剂量的LPS可上调LTAH蛋白含量，但两种剂量的IL-4均可使其降低。较大剂量的LPS、IL-4和IL-10或两种剂量的TNF-α和IL-1β均可使LTCS mRNA表达升高。用两种剂量的IL-1β、IL-4和IL-10、较小剂量的LPS和较大剂量的TNF-α处理后，LTCS蛋白水平升高。两种剂量的LPS以及较大剂量的TNF-α和IL-10均可增加LTB释放。较小剂量的LPS、IL-1β和IL-10或较大剂量的TNF-α和IL-4可刺激LTC释放。较小剂量的TNF-α和IL-1β或两种剂量的IL-4可提高细胞活力。这项工作为LPS、TNF-α、IL-1β、IL-4和IL-10参与猪子宫内膜内皮细胞中LTB和LTC的产生/释放以及上述因素对这些细胞活力的影响提供了新的见解。所使用的细胞模型为进一步确定炎症介质之间的相互作用提供了可能性。
