Cleavage of interleukin 1 beta (IL-1 beta) precursor to produce active IL-1 beta by a conserved extracellular cysteine protease from Streptococcus pyogenes.
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 1 beta precursor (pIL-1 beta) to produce biologically active IL-1 beta. SPE B cleaves pIL-1 beta one residue amino-terminal to the site where a recently characterized endogenous human cysteine protease acts. IL-1 beta resulting from cleavage of pIL-1 beta by SPE B induced nitric oxide synthase activity in vascular smooth muscle cells and killed of the human melanoma A375 line. Two additional naturally occurring SPE B variants cleaved pIL-1 beta in a similar fashion. By demonstrating that SPE B catalyzes the formation of biologically active IL-1 beta from inactive pIL-1 beta, 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.
Kapur
V
V
Department of Pathology, Baylor College of Medicine, Houston, TX 77030.
Majesky
M W
MW
Li
L L
LL
Black
R A
RA
Musser
J M
JM
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D014407:Tumor Cells, Cultured; D014774:Virulence
D007375:Interleukin-1; D011498:Protein Precursors; D011994:Recombinant Proteins; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D003546:Cysteine Endopeptidases