Role of TGF-β1 and TNF-α in IL-1β mediated activation of proMMP-9 in pulmonary artery smooth muscle cells: involvement of an aprotinin sensitive protease

Arch Biochem Biophys. 2011 Sep 1;513(1):61-9. doi: 10.1016/j.abb.2011.06.005. Epub 2011 Jun 22.

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.

MeSH terms

  • Animals
  • Aprotinin / pharmacology*
  • Cattle
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Enzyme Induction / drug effects
  • Enzyme Induction / physiology
  • Enzyme Precursors / biosynthesis*
  • Gelatinases / biosynthesis
  • Interleukin-1beta / metabolism*
  • Interleukin-1beta / pharmacology
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / enzymology*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / enzymology*
  • Pulmonary Artery / cytology
  • Pulmonary Artery / enzymology*
  • RNA, Messenger / biosynthesis
  • Serine Proteinase Inhibitors / pharmacology*
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Enzyme Precursors
  • Interleukin-1beta
  • RNA, Messenger
  • Serine Proteinase Inhibitors
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Aprotinin
  • Gelatinases
  • pro-matrix metalloproteinase 9
  • progelatinase
  • Matrix Metalloproteinase 9