Role of TGF-ß1 and TNF-α in IL-1ß mediated activation of proMMP-9 in pulmonary artery smooth muscle cells: involvement of an aprotinin sensitive protease.

ABSTRACT

We investigated the role of TGF-ß1 and TNF-α in mediating the effect of IL-1ß 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-1ß induces TGF-ß1 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-1ß stimulation, albeit a marked inhibition of TIMP-2 mRNA and protein expression were elicited by TNF-α. Thus, IL-1ß induced stimulation of the two progelatinases occurs via different mechanisms.