Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor.

摘要: Interleukin-1 beta (IL-1 beta) is derived from an inactive precursor by proteolytic cleavage. To study IL-1 processing, we expressed the in Escherichia coli, partially purified it, and used it as a substrate for various potentially relevant protease preparations. The alone was virtually inactive, but incubation with membranes human monocytes or myeloid cell lines yielded 500-fold increase bioactivity. Western blot analysis of incubated material showed that 31,000-Da broken down to three major products, ranging 17,400 about 19,000 Da. most active these products smallest one, co-migrates during electrophoresis mature beta. Four known proteases were also tested their effect on beta, none co-migrated protein. Chymotrypsin Staphylococcus aureus slightly larger which highly active. Elastase trypsin substantially had little activity. identified NH2-terminal sequencing. These results show conclusively proteolysis generates biological activity cleavage must occur close NH2 terminus.