Abstract
We investigated the role of TGF-β1 and TNF-α in mediating the effect of IL-1β in activating proMMP-9 and proMMP-2, and the involvement of an aprotinin sensitive protease in this scenario in bovine pulmonary artery smooth muscle cells. IL-1β induces TGF-β1 mediated stimulation of 92kDa proMMP-9 and 72kDa proMMP-2 mRNA and protein expression; whereas, the elevated level of TNF-α promotes activation of proMMP-9 and proMMP-2. Interestingly, TNF-α induced activation of proMMP-9 appeared to be mediated via a 43kDa aprotinin sensitive protease. TNF-α inhibited aprotinin and TIMP-1 mRNA and protein expression, which apparently facilitated the proteolytic conversion of proMMP-9 to MMP-9 with the involvement of the aprotinin sensitive protease. The aprotinin sensitive protease did not activate proMMP-2 under IL-1β stimulation, albeit a marked inhibition of TIMP-2 mRNA and protein expression were elicited by TNF-α. Thus, IL-1β induced stimulation of the two progelatinases occurs via different mechanisms.
Copyright © 2011 Elsevier Inc. All rights reserved.
MeSH terms
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Animals
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Aprotinin / pharmacology*
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Cattle
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Enzyme Induction / drug effects
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Enzyme Induction / physiology
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Enzyme Precursors / biosynthesis*
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Gelatinases / biosynthesis
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Interleukin-1beta / metabolism*
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Interleukin-1beta / pharmacology
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Matrix Metalloproteinase 9 / biosynthesis*
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / enzymology*
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Myocytes, Smooth Muscle / cytology
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Myocytes, Smooth Muscle / enzymology*
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Pulmonary Artery / cytology
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Pulmonary Artery / enzymology*
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RNA, Messenger / biosynthesis
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Serine Proteinase Inhibitors / pharmacology*
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Transforming Growth Factor beta1 / metabolism*
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Transforming Growth Factor beta1 / pharmacology
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Tumor Necrosis Factor-alpha / metabolism*
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Enzyme Precursors
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Interleukin-1beta
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RNA, Messenger
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Serine Proteinase Inhibitors
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Transforming Growth Factor beta1
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Tumor Necrosis Factor-alpha
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Aprotinin
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Gelatinases
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pro-matrix metalloproteinase 9
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progelatinase
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Matrix Metalloproteinase 9