Activated matrix metalloproteinase-3 (MMP-3) can contribute to periodontal ligament destruction in adult periodontitis. Since MMP-3 has been reported to activate proMMP-8 and -9, it was speculated that gingival tissue fibroblast-derived MMP-3 might, in periodontitis, be responsible for activation of gingival crevicular fluid (GCF) neutrophil-derived proMMP-8 and -9. Immunohistochemistry disclosed MMP-3 in gingival fibroblasts in periodontitis. Cultured gingival fibroblasts released only pro-MMP-3 when stimulated with tumor necrosis factor-α. However, Western blot revealed partially activated MMP-3, MMP-8, and MMP-9 in periodontitis GCF. Active MMP-8 (p < 0.05) and MMP-9 (p < 0.05) correlated with the presence of active MMP-3. It seems that resident gingival fibroblasts produce pro-MMP-3 in GCF, where it becomes activated, probably by cathepsin G or elastase released by neutrophils. Active MMP-3 then activates neutrophil-derived pro-MMP-8 and -9. Different tissue compartments/cells exert co-operative actions in mutual local MMP activation cascades. Chemicals / CAS: collagenase, 37288-86-1, 39433-96-0; gelatinase B, 146480-36-6; gelatinase, 9040-48-6; metalloproteinase, 81669-70-7; procollagenase, 9068-44-4; stromelysin, 79955-99-0; Collagenases, EC 3.4.24.-; Enzyme Precursors; Gelatinases, EC 3.4.24.-; Matrix Metalloproteinase 3, EC 3.4.24.17; Matrix Metalloproteinase 8, EC 3.4.24.34; Matrix Metalloproteinase 9, EC 3.4.24.35; Metalloendopeptidases, EC 3.4.24.-; procollagenase, EC 3.4.24.-; progelatinase, EC 3.4.24.-