ROLE OF METALLOPROTEASES IN THE RELEASE OF THE IL-1 TYPE-II DECOY RECEPTOR

The IL-1 type II receptor (decoy RII) is a nonsignaling molecule the o nly established function of which is to capture IL-1 and prevent it fr om interacting with signaling receptor. The decoy RII is released in a regulated way from the cell surface. Here, we reported that hydroxami c acid inhibitors of matrix metalloproteases inhibit different pathway s of decoy RII release, including the following: (a) the slow (18 h) g ene expression dependent release from monocytes and polymorphonuclear cells exposed to dexamethasone; (b) rapid release (minutes) from myelo monocytic cells exposed to tumor necrosis factor, chemoattractants, or phorbol myristate acetate; (c) phorbol myristate acetate-induced rele ase from decoy RII-transfected fibroblasts and B cells. Inhibition of release was associated with increased surface expression of decoy RII. Inhibitors of other protease classes did not substantially affect rel ease. However, serine protease inhibitors increased the molecular mass of the decoy RII released from polymorphonuclear cells from 45 to 60 kDa. Thus, irrespective of the pathway responsible for release and of the cellular context, matrix metalloproteases, rather than differentia l splicing, play a key role in production of soluble decoy RII.