Yamada M, Ichinowatari G, Tanimoto A, Yaginuma H, Ohuchi K
Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
Life Sci. 1998;62(20):PL 297-302. doi: 10.1016/s0024-3205(98)00156-8.
When rat peritoneal macrophages were incubated in medium containing thapsigargin, tumor necrosis factor-alpha (TNF-alpha) production was increased time-dependently. In the presence of SK&F 98625, a CoA-independent transacylase inhibitor, the thapsigargin-induced TNF-alpha production was inhibited dose-dependently. Platelet-activating factor (PAF) and prostaglandin E2 (PGE2) production were also inhibited by SK&F 98625. The SK&F 98625-induced inhibition of TNF-alpha production was not prevented by addition of PGE2. PAF antagonists such as E6123, L-652,731 and CV-6209 partially inhibited the thapsigargin-induced TNF-alpha production, suggesting that concurrently produced PAF in thapsigargin-stimulated macrophages up-regulates TNF-alpha production. The inhibition by SK&F 98625 of thapsigargin-induced TNF-alpha production might be partly due to the inhibition of PAF production.
当大鼠腹膜巨噬细胞在含有毒胡萝卜素的培养基中孵育时，肿瘤坏死因子-α（TNF-α）的产生呈时间依赖性增加。在存在SK&F 98625（一种不依赖辅酶A的转酰基酶抑制剂）的情况下，毒胡萝卜素诱导的TNF-α产生呈剂量依赖性受到抑制。血小板活化因子（PAF）和前列腺素E2（PGE2）的产生也受到SK&F 98625的抑制。添加PGE2并不能阻止SK&F 98625对TNF-α产生的抑制作用。PAF拮抗剂如E6123、L-652,731和CV-6209部分抑制了毒胡萝卜素诱导的TNF-α产生，这表明在毒胡萝卜素刺激的巨噬细胞中同时产生的PAF上调了TNF-α的产生。SK&F 98625对毒胡萝卜素诱导的TNF-α产生的抑制作用可能部分归因于对PAF产生的抑制。
