Inactivation of tissue inhibitor of metalloproteinases-1 (TIMP-1) by Porphyromonas gingivalis

In response to periodontal inflammation, host cells release matrix metallop roteinases (MMPs) that contribute to periodontal tissue breakdown unless th e tissue inhibitors of metalloproteinases (TIMPs) neutralize their activity . In this study, the capacity of Porphyromonas gingivalis to inactivate TIM P-1 was investigated. Proteolytic digestion of TIMP-1 was monitored by SDS- PAGE and Western immunoblotting. Planktonic cells and biofilms of R gingiva lis degraded TIMP-1 with production of several lower molecular mass fragmen ts. Incorporation of human serum in the assay mixture had no effect on the degradation of TIMP-1 by P. gingivalis, whereas a cysteine proteinase inhib itor caused a complete inhibition. Using a fluorogenic assay, it was found that TIMP-1 treated with P. gingivalis lost its capacity to inhibit MMP-9 a ctivity. This study revealed the potential of P, gingivalis to inactivate T IMP-1 through proteolytic degradation. This phenomenon may contribute to in creasing significantly the level of active MMPs in affected periodontal sit es and subsequently favor tissue destruction. (C) 2001 Federation of Europe an Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.