PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-2 IS A MAJOR PROTEIN-INDUCED IN HUMAN FIBROBLASTS AND SK-MEL-109 MELANOMA-CELLS BY TUMOR-NECROSIS-FACTOR

Tumor necrosis factor (TNF) induces the synthesis of two proteins of Mr 42 and 36 kDa in human fibroblasts and SK‐MEL‐109 melanoma cells. To identify these proteins, a λgt10 cDNA library was prepared from the mRNA of TNF‐treated SK‐MEL‐109 cells. By screening this library, we found a cDNA that preferentially hybridized to TNF‐induced RNA. Hybrid‐selected mRNA was translated into a protein of 42 kDa; cDNA sequence analysis followed by a comparison with other known protein sequences identified this protein with plasminogen activator inhibitor, type‐2 (PAI‐2). After removal of TNF, PAI‐2 mRNA turned over rapidly, with an apparent half‐life of ∼ 2.5 h. Addition of dexamethasone increased the turnover of this mRNA, suggesting that the level of PAI‐2 mRNA could be regulated post‐transcriptionally by glucocorticoids. PAI‐2 was not secreted, but accumulated in fibroblasts continuously treated with TNF. Copyright © 1990 Wiley‐Liss, Inc.