| First Author | Mahmoodi M | Year | 2005 |
| Journal | Am J Pathol | Volume | 166 |
| Issue | 6 | Pages | 1733-40 |
| PubMed ID | 15920158 | Mgi Jnum | J:98813 |
| Mgi Id | MGI:3579967 | Doi | 10.1016/S0002-9440(10)62483-2 |
| Citation | Mahmoodi M, et al. (2005) Lack of tissue inhibitor of metalloproteinases-3 results in an enhanced inflammatory response in antigen-induced arthritis. Am J Pathol 166(6):1733-40 |
| abstractText | Tissue inhibitor of metalloproteinases-3 (TIMP-3) is known to inhibit matrix metalloproteinases, aggrecanases, and tumor necrosis factor (TNF)-alpha-converting enzyme (TACE, ADAM17). These metalloproteases participate in different aspects of joint destruction in inflammatory arthritis. To determine the relative importance of this inhibitor in joint pathology, wild-type and Timp3(-/-) mice were immunized with methylated bovine serum albumin followed by arthritis induction by intra-articular injection of the same antigen. Animals were monitored for up to 14 days after challenge, and joint tissues were analyzed by routine and Safranin O staining and for the presence of aggrecan neoepitopes produced by metalloprotease cleavage. Serum TNF-alpha was measured by immunoassay. Compared to wild-type animals, Timp3(-/-) mice showed a dramatic increase in the initial inflammatory response to intra-articular antigen injection, and serum TNF-alpha levels were greatly elevated in the Timp3(-/-) animals after immunization. However, these differences in clinical features disappeared by days 7 to 14. No difference in Safranin O staining or aggrecan cleavage site neoepitope abundance was seen. Thus, in inflammatory joint disease TIMP-3 likely dampens the inflammatory response of TNF-alpha by reducing ADAM17 activity. |
