Department of Veterinary-Physiology and -Biochemistry, Justus Liebig University Giessen, Frankfurter Strasse 100, 35392, Giessen, Germany.
Inflamm Res. 2022 Feb;71(2):187-190. doi: 10.1007/s00011-021-01534-2. Epub 2021 Dec 23.
We investigated whether it is possible to induce a state of "LPS-sensitization" in neurons of primary cultures from rat dorsal root ganglia by pre-treatment with ultra-low doses of LPS.
DRG primary cultures were pre-treated with low to ultra-low doses of LPS (0.001-0.1 µg/ml) for 18 h, followed by a short-term stimulation with a higher LPS-dose (10 µg/ml for 2 h). TNF-α in the supernatants was measured as a sensitive read out. Using the fura-2 340/380 nm ratio imaging technique, we further investigated the capsaicin-evoked Ca-signals in neurons from DRG, which were pre-treated with a wide range of LPS-doses.
Release of TNF-α evoked by stimulation with 10 µg/ml LPS into the supernatant was not significantly modified by pre-exposure to low to ultra-low LPS-doses. Capsaicin-evoked Ca-signals were significantly enhanced by pre-treatment with LPS doses being above a certain threshold.
Ultra-low doses of LPS, which per se do not evoke a detectable inflammatory response, are not sufficient to sensitize neurons (Ca-responses) and glial elements (TNF-α-responses) of the primary afferent somatosensory system.
我们研究了通过用极低剂量的脂多糖(LPS)预处理是否可以诱导大鼠背根神经节原代培养神经元中的“LPS 敏化”状态。
用低至超低剂量的 LPS(0.001-0.1μg/ml)预处理 DRG 原代培养物 18 小时,然后用更高剂量的 LPS(10μg/ml,持续 2 小时)进行短期刺激。测量上清液中的 TNF-α作为敏感读出。使用 fura-2 340/380nm 比值成像技术,我们进一步研究了用广泛范围的 LPS 剂量预处理后的 DRG 神经元中辣椒素诱发的 Ca 信号。
用 10μg/ml LPS 刺激引起的 TNF-α释放,用低至超低 LPS 剂量预先暴露不会显著改变。用高于一定阈值的 LPS 剂量预处理会显著增强辣椒素诱发的 Ca 信号。
本身不会引起可检测的炎症反应的超低剂量 LPS 不足以敏化初级感觉传入躯体神经系统的神经元(Ca 反应)和神经胶质细胞(TNF-α 反应)。