Benito E, Bosch M A
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, Universidad Complutense, Madrid, Spain.
Mol Cell Biochem. 1998 Dec;189(1-2):169-76. doi: 10.1023/a:1006997731607.
Tumor necrosis factor alpha and interleukin-1beta increase surfactant secretion in type II pneumocytes in a time- and dose-dependent manner. This stimulatory effect was additive to that of lipopolysaccharide, suggesting that cytokines and lipopolysaccharide may exert their actions through different signal transduction pathways. Tumor necrosis factor alpha and interleukin-1beta did not modify the increase on phosphatidylcholine secretion induced by the direct protein kinase C activator tetradecanoylphorbol 13-acetate, whereas this effect was inhibited by the protein kinase C inhibitors bisindolylmaleimide (2 x 10(-6) M) and 1-(5-isoquinolinylsulphonyl)-2-methyl piperazone (10(-4) M). In addition, the stimulatory effect of tumor necrosis factor alpha and interleukin-1beta was not suppressed by the intracellular Ca2+ chelator BAPTA (5 x 10(-6) M) or by KN-62 (3 x 10(-5) M), a specific inhibitor of Ca2+-calmodulin-dependent protein kinase. These results suggest that tumor necrosis factor alpha or interleukin-1beta stimulate phosphatidylcholine secretion via protein kinase C activation in a Ca2+-independent manner.
肿瘤坏死因子α和白细胞介素-1β以时间和剂量依赖的方式增加II型肺细胞表面活性剂的分泌。这种刺激作用与脂多糖的作用相加，表明细胞因子和脂多糖可能通过不同的信号转导途径发挥作用。肿瘤坏死因子α和白细胞介素-1β不会改变直接蛋白激酶C激活剂十四酰佛波醇13-乙酸酯诱导的磷脂酰胆碱分泌增加，而蛋白激酶C抑制剂双吲哚马来酰亚胺（2×10⁻⁶ M）和1-（5-异喹啉磺酰基）-2-甲基哌嗪（10⁻⁴ M）可抑制这种作用。此外，细胞内Ca²⁺螯合剂BAPTA（5×10⁻⁶ M）或Ca²⁺-钙调蛋白依赖性蛋白激酶的特异性抑制剂KN-62（3×10⁻⁵ M）不会抑制肿瘤坏死因子α和白细胞介素-1β的刺激作用。这些结果表明，肿瘤坏死因子α或白细胞介素-1β通过蛋白激酶C激活以不依赖Ca²⁺的方式刺激磷脂酰胆碱分泌。
