Document Type



Injury to a peripheral nerve is followed by a remodeling process consisting of axonal degenera- tion and regeneration. It is not known how Schwann cell–derived basement membrane is pre- served after injury or what role matrix metalloproteinases (MMPs) and their inhibitors play in axonal degeneration and regeneration. We showed that the MMPs gelatinase B (MMP-9), stromelysin-1 (MMP-3), and the tissue inhibitor of MMPs (TIMP)-1 were induced in crush and distal segments of mouse sciatic nerve after injury. TIMP-1 inhibitor activity was present in excess of proteinase activity in extracts of injured nerve. TIMP-1 protected basement mem- brane type IV collagen from degradation by exogenous gelatinase B in cryostat sections of nerve in vitro. In vivo, during the early phase (1 d after crush) and later phase (4 d after crush) after injury, induction of TNF- a and TGF- B 1 mRNAs, known modulators of TIMP-1 ex- pression, were paralleled by an upregulation of TIMP-1 and gelatinase B mRNAs. At 4 days after injury, TIMP-1, gelatinase B, and TNF- a mRNAs were localized to infiltrating mac- rophages and Schwann cells in the regions of nerve infiltrated by elicited macrophages. TIMP-1 and cytokine mRNA expression was upregulated in undamaged nerve explants incubated with medium conditioned by macrophages or containing the cytokines TGF- B 1, TNF- a , and IL-1 a . These results show that TIMP-1 may protect basement membrane from uncontrolled degrada- tion after injury and that cytokines produced by macrophages may participate in the regulation of TIMP-1 levels during nerve repair.


Obstetrics and Gynecology


Copyright (1996) The Rockefeller University Press. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the Rockefeller University Press. This article is the publisher’s version (The Rockefeller University Press), previously appearing in J. EXP. MED. (184, 1996, pp. 2311-2326). Also available online at