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 1β precursor (pIL-1β) to produce biologically active IL-1β. SPE B cleaves pIL- 1β one residue amino-terminal to the site where a recently characterized endogenous human cysteine protease acts. IL-1β resulting from cleavage of pIL-1β 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-1β in a similar fashion. By demonstrating that SPE B catalyzes the formation of biologically active IL- 1β from inactive pIL-1β, 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.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1993|
All Science Journal Classification (ASJC) codes