Björnberg F, Lantz M, Gullberg U
Department of Medicine, University of Lund, Sweden.
Scand J Immunol. 1995 Oct;42(4):418-24. doi: 10.1111/j.1365-3083.1995.tb03675.x.
The proteolytic processing of the two TNF receptors (TNF-R55 and TNF-R75) into soluble forms was investigated in the myeloid cell lines U-937 and THP-1. Phorbol myristate acetate (PMA) rapidly stimulated release of soluble forms of both TNF-receptors. Incubations were made with PMA and protease inhibitors directed against different target protease groups. The serineprotease inhibitors TPCK and dichloroisocoumarin and the metalloprotease inhibitor 1,10-phenanthroline reduced PMA-induced release of both soluble receptor forms with about 60-70%. Furthermore, 1,10-phenanthroline also reduced PMA-induced down-regulation of TNF-receptors in both cell lines as judged by TNF-binding to cells. Reduced down-regulation and TNF-receptor shedding by 1,10-phenanthroline was reversed by Zn2+, indicating involvement of a Zn(2+)-dependent metalloprotease. Thus, both serine proteases and metalloproteases are involved in the processing of TNF-receptors.
在髓系细胞系U-937和THP-1中研究了两种肿瘤坏死因子受体（TNF-R55和TNF-R75）向可溶性形式的蛋白水解加工过程。佛波酯肉豆蔻酸酯乙酸酯（PMA）迅速刺激两种TNF受体可溶性形式的释放。用PMA和针对不同靶蛋白酶组的蛋白酶抑制剂进行孵育。丝氨酸蛋白酶抑制剂TPCK和二氯异香豆素以及金属蛋白酶抑制剂1,10-菲咯啉使PMA诱导的两种可溶性受体形式的释放减少约60-70%。此外，通过TNF与细胞的结合判断，1,10-菲咯啉还减少了PMA诱导的两种细胞系中TNF受体的下调。1,10-菲咯啉导致的下调减少和TNF受体脱落可被Zn2+逆转，表明涉及一种Zn(2+)依赖性金属蛋白酶。因此，丝氨酸蛋白酶和金属蛋白酶均参与TNF受体的加工过程。
