Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase.
Secretory granules of human dermal mast cells contain a chymotrypsin-like serine proteinase called chymase. In this study, we demonstrate that the inactive cytokine, 31 kD interleukin 1 beta (IL-1 beta), can be converted rapidly to an 18 kD biologically active species by human mast cell chymase. The product formed is three amino acids longer at the amino terminus than the mature IL-1 beta produced by peripheral blood mononuclear cells and has comparable biological activity. Because chymase is a secretory granule constituent, it is likely to be released into the surrounding tissue when mast cells degranulate. It is also known that non-bone marrow derived cells resident in skin (keratinocytes, fibroblasts) produce but do not process 31 kD IL-1 beta. In this context, chymase may be a potent activator of locally produced 31 kD IL-1 beta. Mast cells lie in close apposition to blood vessels in dermis; therefore, chymase mediated conversion of 31 kD IL-1 beta might be expected to have a critical role in the initiation of the inflammatory response in skin.
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
H
H
Mizutani
N
N
Schechter
G
G
Lazarus
R A
RA
Black
T S
TS
Kupper
D000595:Amino Acid Sequence; D053818:Chymases; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008407:Mast Cells / Q000201:enzymology*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D012867:Skin / Q000201:enzymology; D013601:T-Lymphocytes / Q000276:immunology
D007375:Interleukin-1; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D053818:Chymases