Herzog Christian, Kaushal Gur P, Haun Randy S
Department of Pathology, University of Arkansas for Medical Sciences, 4301 West Markham Street #753, Little Rock, AR 72205, USA.
Cytokine. 2005 Sep 7;31(5):394-403. doi: 10.1016/j.cyto.2005.06.012.
Interleukin-1beta (IL-1beta) is a proinflammatory cytokine that is synthesized as an inactive precursor molecule that must be proteolytically processed to generate the biologically active form. Maturation of the precursor is primarily performed by caspase-1, an intracellular cysteine protease; however, processing by other proteases has been described. Meprins are cell surface and secreted metalloproteases expressed by renal and intestinal brush-border membranes, leukocytes, and cancer cells. In this study we show that purified recombinant meprin B can process the interleukin-1beta precursor to a biologically active form. Amino-terminal sequencing and mass spectrometry analysis of the product of digestion by activated meprin B determined that proteolytic cleavage resulted in an additional six amino acids relative to the site utilized by caspase-1. The biological activity of the meprin B-cleaved cytokine was confirmed by measuring the proliferative response of helper T-cells. These results suggest that meprin may play an important role in activation of this proinflammatory cytokine in various pathophysiological conditions.
白细胞介素-1β（IL-1β）是一种促炎细胞因子，它作为一种无活性的前体分子合成，必须经过蛋白水解加工才能产生生物活性形式。前体的成熟主要由细胞内半胱氨酸蛋白酶caspase-1完成；然而，也有其他蛋白酶进行加工的报道。膜金属蛋白酶是由肾和肠刷状缘膜、白细胞及癌细胞表达的细胞表面和分泌型金属蛋白酶。在本研究中，我们发现纯化的重组膜金属蛋白酶B可将白细胞介素-1β前体加工成生物活性形式。对活化的膜金属蛋白酶B消化产物进行氨基末端测序和质谱分析，确定蛋白水解切割相对于caspase-1所利用的位点产生了另外六个氨基酸。通过测量辅助性T细胞的增殖反应证实了膜金属蛋白酶B切割的细胞因子的生物活性。这些结果表明，膜金属蛋白酶可能在各种病理生理条件下该促炎细胞因子的激活中发挥重要作用。
