Chen C-C, Lee J-J, Tsai P-S, Lu Y-T, Huang C-L, Huang C-J
Nursing and Management College [corrected] Taipei, Taiwan.
Acta Anaesthesiol Scand. 2006 May;50(5):604-12. doi: 10.1111/j.1399-6576.2006.00750.x.
Platonin, a cyanine photosensitizing dye, is a potent immunomodulator that suppresses acute inflammation. Platonin not only inhibits interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha production but also improves circulatory failure in septic rats. In addition, platonin reduces plasma nitric oxide (NO) formation during sepsis. However, the effects of platonin on inducible NO synthase (iNOS) and cationic amino-acid transporter (including CAT-2, CAT-2 A, and CAT-2B) expressions during sepsis remain uninvestigated.
Five groups of confluent murine macrophages (RAW264.7 cells) were randomly allocated to receive a 1-h pretreatment of one of five doses of platonin (0.1 microM, 1 microM, 10 microM, 100 microM, or 1000 microM) followed by lipopolysaccharide (LPS; 100 ng ml(-1)). For negative, positive, and platonin control, three other groups of cell cultures were randomly allocated to receive phosphate-buffered saline, LPS, or platonin (1000 microM). The cultures were harvested after exposing them to LPS for 18 h or a comparable duration in those groups without LPS. NO production, L-arginine transport, and expression of the relevant enzymes were then evaluated.
Platonin significantly attenuated LPS-induced up-regulation of iNOS expression and NO production in stimulated murine macrophages in a dose-dependent manner. Platonin also significantly inhibited up-regulation of CAT-2 and CAT-2B expression as well as L-arginine transport in LPS-stimulated murine macrophages in a dose-dependent manner. In contrast, CAT-2 A expression in murine macrophages was not affected by LPS and/or platonin.
Platonin attenuates NO production and L-arginine transport in LPS-stimulated murine macrophages possibly through inhibiting iNOS, CAT-2, and CAT-2B expression.
普拉托宁是一种花菁类光敏染料，是一种有效的免疫调节剂，可抑制急性炎症。普拉托宁不仅能抑制白细胞介素（IL）-1β、IL-6和肿瘤坏死因子（TNF）-α的产生，还能改善脓毒症大鼠的循环衰竭。此外，普拉托宁可减少脓毒症期间血浆一氧化氮（NO）的形成。然而，脓毒症期间普拉托宁对诱导型一氧化氮合酶（iNOS）和阳离子氨基酸转运体（包括CAT-2、CAT-2A和CAT-2B）表达的影响仍未得到研究。
将五组汇合的小鼠巨噬细胞（RAW264.7细胞）随机分为五组，分别接受五种剂量（0.1微摩尔/升、1微摩尔/升、10微摩尔/升、100微摩尔/升或1000微摩尔/升）普拉托宁中的一种进行1小时预处理，随后给予脂多糖（LPS；100纳克/毫升）。对于阴性、阳性和普拉托宁对照组，将另外三组细胞培养物随机分为接受磷酸盐缓冲盐水、LPS或普拉托宁（1000微摩尔/升）。在将细胞培养物暴露于LPS 18小时后或在未接受LPS的组中暴露于相当长的时间后收获细胞培养物。然后评估NO的产生、L-精氨酸转运以及相关酶的表达。
普拉托宁以剂量依赖的方式显著减弱LPS诱导的受刺激小鼠巨噬细胞中iNOS表达上调和NO产生。普拉托宁还以剂量依赖的方式显著抑制LPS刺激的小鼠巨噬细胞中CAT-2和CAT-2B表达上调以及L-精氨酸转运。相比之下，小鼠巨噬细胞中CAT-2A的表达不受LPS和/或普拉托宁的影响。
普拉托宁可能通过抑制iNOS、CAT-2和CAT-2B的表达来减弱LPS刺激的小鼠巨噬细胞中NO的产生和L-精氨酸转运。
