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

We investigated the role of TGF-beta 1 and TNF-alpha in mediating the effect of IL-1 beta 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-1 beta induces TGF-beta 1 mediated stimulation of 92 kDa proMMP-9 and 72 kDa proMMP-2 mRNA and protein expression; whereas, the elevated level of TNF-alpha promotes activation of proMMP-9 and proMMP-2. Interestingly, TNF-alpha induced activation of proMMP-9 appeared to be mediated via a 43 kDa aprotinin sensitive protease. TNF-alpha 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-1 beta stimulation, albeit a marked inhibition of TIMP-2 mRNA and protein expression were elicited by TNF-alpha. Thus, IL-1 beta induced stimulation of the two progelatinases occurs via different mechanisms. (C) 2011 Elsevier Inc. All rights reserved.