CLEAVAGE OF INTERLEUKIN-1-BETA (IL-1-BETA) PRECURSOR TO PRODUCE ACTIVE IL-1-BETA BY A CONSERVED EXTRACELLULAR CYSTEINE PROTEASE FROM STREPTOCOCCUS-PYOGENES
CLEAVAGE OF INTERLEUKIN-1-BETA (IL-1-BETA) PRECURSOR TO PRODUCE ACTIVE IL-1-BETA BY A CONSERVED EXTRACELLULAR CYSTEINE PROTEASE FROM STREPTOCOCCUS-PYOGENES
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DOI：
10.1073/pnas.90.16.7676
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发表时间：
1993-08-15
影响因子：
11.1
通讯作者：
MUSSER, JM
中科院分区：
文献类型：
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作者：
KAPUR, V;MAJESKY, MW;MUSSER, JM
产热链球菌外毒素B(SPE B)是一种由人类致病菌化脓性链球菌表达的保守的胞外半胱氨酸蛋白酶，经纯化后可裂解失活的人白细胞介素1β前体(PIL-1β)，产生具有生物活性的IL-1β。SPE B将PIL-1β1残基的氨基末端切割到最近确定的内源性人半胱氨酸蛋白酶的作用部位。SPE B裂解PIL-1β产生的IL-1β诱导血管平滑肌细胞和人黑色素瘤A375细胞杀伤细胞的一氧化氮合酶活性。另外两个自然产生的SPE B变体以类似的方式切割PIL-1β。通过证明SPE B催化非活性的IL-1β形成生物活性的IL-1β，我们的数据为微生物发病机制中的一个新兴主题添加了进一步的维度，即细菌和病毒毒力因子直接作用于宿主细胞因子途径。这些数据还有助于扩大证明微生物胞外半胱氨酸蛋白酶在宿主-寄生虫相互作用中的重要作用的文献。
Streptococcal pyrogenic exotoxin B (SPE B), a conserved extracellular cysteine protease expressed by the human pathogenic bacterium Streptococcus pyogenes, was purified and shown to cleave inactive human interleukin 1beta precursor (pIL-1beta) to produce biologically active IL-1beta. SPE B cleaves pIL-1beta one residue amino-terminal to the site where a recently characterized endogenous human cysteine protease acts. IL-1beta resulting from cleavage of pIL-1beta by SPE B induced nitric oxide synthase activity in vascular smooth muscle cells and killed cells of the human melanoma A375 line. Two additional naturally occurring SPE B variants cleaved pIL-1beta in a similar fashion. By demonstrating that SPE B catalyzes the formation of biologically active IL-1beta from inactive pIL-1beta, our data add a further dimension to an emerging theme in microbial pathogenesis that bacterial and viral virulence factors act directly on host cytokine pathways. The data also contribute to an enlarging literature demonstrating that microbial extracellular cysteine proteases are important in host-parasite interactions.