Arai T, Hiromatsu K, Kobayashi N, Takano M, Ishida H, Nimura Y, Yoshikai Y
Laboratory of Host Defense and Germfree Life, Nagoya University School of Medicine, Japan.
J Immunol. 1995 Dec 15;155(12):5743-9.
The effects of exogenous cAMP, dibutyryl cAMP (DBcAMP) on LPS-induced liver injury were examined in mice made hypersensitive to LPS by treatment with i.v. injection of Propionibacterium acnes. In vivo administration of DBcAMP significantly protected P. acnes-treated mice from LPS-induced liver injury, including apoptosis of hepatocytes. DBcAMP significantly increased circulating IL-10 level in correlation with suppression of the TNF-alpha level after LPS challenge in P. acnes-treated mice. Treatment with anti-IL-10 mAb abrogated the protective effect of DBcAMP on LPS-induced liver injury. Similar to in vivo findings, addition to DBcAMP to in vitro culture of liver adherent cells from P. acnes-treated mice enhanced IL-10 synthesis after LPS stimulation. These results suggest that the increment in IL-10 production by liver adherent cells is involved in the protective effect of DBcAMP on LPS-induced inflammatory liver injury.
通过静脉注射痤疮丙酸杆菌使小鼠对脂多糖（LPS）致敏，在此基础上研究了外源性环磷酸腺苷（cAMP）、二丁酰环磷酸腺苷（DBcAMP）对LPS诱导的肝损伤的影响。在体内给予DBcAMP可显著保护经痤疮丙酸杆菌处理的小鼠免受LPS诱导的肝损伤，包括肝细胞凋亡。在经痤疮丙酸杆菌处理的小鼠中，LPS攻击后，DBcAMP显著提高循环中白细胞介素-10（IL-10）水平，同时抑制肿瘤坏死因子-α（TNF-α）水平。用抗IL-10单克隆抗体处理可消除DBcAMP对LPS诱导的肝损伤的保护作用。与体内研究结果相似，在经痤疮丙酸杆菌处理的小鼠肝脏贴壁细胞的体外培养中加入DBcAMP可增强LPS刺激后的IL-10合成。这些结果表明，肝脏贴壁细胞产生IL-10的增加与DBcAMP对LPS诱导的炎症性肝损伤的保护作用有关。
