Björnberg F, Lantz M, Olsson I, Gullberg U
Department of Medicine, University of Lund, Sweden.
Lymphokine Cytokine Res. 1994 Jun;13(3):203-11.
The two tumor necrosis factor (TNF) receptors (TNF-R55 and TNF-R75) can release soluble TNF-binding proteins (TNF-R55-BP and TNF-R75-BP) by proteolytic cleavage. The proteolytic processing of the TNF receptors was investigated in monoblastic THP-1 and promyelocytic HL-60-10 leukemic cell lines. The release of soluble forms of both receptors was rapidly stimulated by staurosporine-sensitive protein kinase C activation by phorbol myristate acetate (PMA) and more slowly stimulated by TNF. No receptor release was seen below a temperature of 16 degrees C. NH4Cl (10 mmol/liter) and monensin (1 mumol/liter), known to increase intracellular pH, inhibited to some extent PMA- and TNF-induced release of both TNF-R55-BP and TNF-R75-BP. The inhibitory effect of monensin might be explained by a diminished translocation of newly synthesized receptor to the plasma membrane. The weak inhibitory effect of NH4Cl on PMA-induced release of soluble receptor forms could be due to effects on a pH-sensitive compartment. PMA-induced down-regulation of receptors was not dependent on acidity as it occurred also in the presence of monensin and NH4Cl when the release of TNF-BPs is partially blocked. Dibutyryl cAMP inhibited the PMA-induced release of TNF-R55-BP but not of TNF-R75-BP in both cell lines investigated. In addition, dibutyryl cAMP alone stimulated the release of both receptors but only in THP-1 cells. Our data show that the generation of soluble forms of both TNF receptors can be regulated by both PKC and PKA.
两种肿瘤坏死因子（TNF）受体（TNF-R55和TNF-R75）可通过蛋白水解切割释放可溶性TNF结合蛋白（TNF-R55-BP和TNF-R75-BP）。在单核细胞THP-1和早幼粒细胞HL-60-10白血病细胞系中研究了TNF受体的蛋白水解过程。佛波酯肉豆蔻酸酯乙酸酯（PMA）激活对星孢菌素敏感的蛋白激酶C可迅速刺激两种受体可溶性形式的释放，而TNF刺激则较为缓慢。在16摄氏度以下的温度未见受体释放。已知可提高细胞内pH值的氯化铵（10 mmol/升）和莫能菌素（1 μmol/升）在一定程度上抑制PMA和TNF诱导的TNF-R55-BP和TNF-R75-BP的释放。莫能菌素的抑制作用可能是由于新合成的受体向质膜的转运减少所致。氯化铵对PMA诱导的可溶性受体形式释放的微弱抑制作用可能是由于对pH敏感区室的影响。PMA诱导的受体下调不依赖于酸度，因为当TNF-BPs的释放被部分阻断时，在莫能菌素和氯化铵存在的情况下也会发生这种下调。在两种研究的细胞系中，二丁酰环磷腺苷抑制PMA诱导的TNF-R55-BP释放，但不抑制TNF-R75-BP释放。此外，单独的二丁酰环磷腺苷可刺激两种受体的释放，但仅在THP-1细胞中。我们的数据表明，两种TNF受体可溶性形式的产生可受蛋白激酶C和蛋白激酶A的调节。
