Taguchi I, Oka K, Kitamura K, Sugiura M, Oku A, Matsumoto M
Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., Osaka, Japan.
Inflamm Res. 1999 Jul;48(7):380-5. doi: 10.1007/s000110050475.
To study the effect of cellular cAMP-increasing agents on Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS)-induced mouse hepatitis.
Male BALB/c mice were used. Macrophages/Kupffer cells isolated from P. acnes-primed murine liver were used for the in vitro study.
Type IV phosphodiesterase (PDE)-specific inhibitor, rolipram, was administered (10, 30 mg/kg, p. o.). Dibutyryl cyclic AMP (dbcAMP) was injected (10, 100 mg/kg, i.p.) into the mice.
Plasma TNFalpha estimated by the use of an L-929 cell cytotoxic assay and plasma transaminase activities were measured for the in vivo study. The LPS-induced production of TNFalpha in vitro from the cultured macrophage/Kupffer cells was determined by ELISA.
Rolipram suppressed the elevation of plasma transaminases induced by injection of LPS, and dbcAMP had a tendency to suppress them. Both agents attenuated the LPS-induced release of TNFalpha in vivo, and suppressed the TNFalpha production from the cultured macrophage/Kupffer cells.
These results suggest that rolipram and dbcAMP have potential to inhibit TNFalpha production from activated macrophage/Kupffer cells, and it may be partially involved in the protecting effect in the P. acnes/LPS hepatitis model.
研究细胞内环磷酸腺苷（cAMP）升高剂对痤疮丙酸杆菌（P. acnes）和脂多糖（LPS）诱导的小鼠肝炎的影响。
使用雄性BALB/c小鼠。从经痤疮丙酸杆菌致敏的小鼠肝脏中分离出的巨噬细胞/库普弗细胞用于体外研究。
给予IV型磷酸二酯酶（PDE）特异性抑制剂咯利普兰（10、30mg/kg，口服）。将二丁酰环磷酸腺苷（dbcAMP）（10、100mg/kg，腹腔注射）注入小鼠体内。
通过L-929细胞细胞毒性试验评估血浆肿瘤坏死因子α（TNFα），并测量血浆转氨酶活性用于体内研究。通过酶联免疫吸附测定法（ELISA）测定培养的巨噬细胞/库普弗细胞在体外由LPS诱导产生的TNFα。
咯利普兰抑制了注射LPS诱导的血浆转氨酶升高，dbcAMP有抑制它们的趋势。两种药物均减弱了LPS在体内诱导的TNFα释放，并抑制了培养的巨噬细胞/库普弗细胞产生TNFα。
这些结果表明，咯利普兰和dbcAMP有潜力抑制活化的巨噬细胞/库普弗细胞产生TNFα，并且这可能部分参与了痤疮丙酸杆菌/LPS肝炎模型中的保护作用。
