Abstract
Matrix metalloproteinases (MMPs) and interleukin 1 (IL-1) are implicated in inflammation and tissue destruction, where IL-1 is a potent stimulator of connective tissue cells to produce the extracellular matrix-degrading MMPs. Here, we report that IL-1beta, but not IL-1alpha, is degraded by MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), and MMP-9 (gelatinase B). This degradation was effectively blocked by tissue inhibitor of metalloproteinases (TIMP)-1. When IL-1beta was treated with MMPs it lost the ability to enhance the synthesis of prostaglandin E2 and pro-MMP-3 in human fibroblasts. The primary cleavage site of IL-1beta by MMP-2 was identified at the Glu25-Leu26 bond. These results suggest that IL-1beta stimulates connective tissue cells to produce MMPs, but activated MMPs in turn negatively regulate the activity of IL-1beta.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Cell Line
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Collagenases / metabolism*
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Dinoprostone / biosynthesis
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Enzyme Activation
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Fibrosarcoma
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Gelatinases / metabolism*
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Glycoproteins / pharmacology
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Humans
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Inflammation
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Interleukin-1 / chemistry
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Interleukin-1 / metabolism*
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Interleukin-1 / pharmacology
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Kinetics
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Matrix Metalloproteinase 1
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 9
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Metalloendopeptidases / metabolism*
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Molecular Sequence Data
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Phenylmercuric Acetate / analogs & derivatives
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Phenylmercuric Acetate / pharmacology
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Substrate Specificity
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Sulfhydryl Reagents / pharmacology
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Tissue Inhibitor of Metalloproteinases
Substances
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Glycoproteins
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Interleukin-1
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Sulfhydryl Reagents
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Tissue Inhibitor of Metalloproteinases
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4-aminophenylmercuriacetate
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Collagenases
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Gelatinases
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Metalloendopeptidases
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Matrix Metalloproteinase 1
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Dinoprostone
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Phenylmercuric Acetate