PMID- 8976186 OWN - NLM STAT- MEDLINE DCOM- 19970130 LR - 20240214 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 184 IP - 6 DP - 1996 Dec 1 TI - Basement membrane and repair of injury to peripheral nerve: defining a potential role for macrophages, matrix metalloproteinases, and tissue inhibitor of metalloproteinases-1. PG - 2311-26 AB - Injury to a peripheral nerve is followed by a remodeling process consisting of axonal degeneration and regeneration. It is not known how Schwann cell-derived basement membrane is preserved 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 membrane 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-alpha and TGF-beta 1 mRNAs, known modulators of TIMP-1 expression, were paralleled by an upregulation of TIMP-1 and gelatinase B mRNAs. At 4 days after injury, TIMP-1, gelatinase B, and TNF-alpha mRNAs were localized to infiltrating macrophages 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-beta 1, TNF-alpha, and IL-1 alpha. These results show that TIMP-1 may protect basement membrane from uncontrolled degradation after injury and that cytokines produced by macrophages may participate in the regulation of TIMP-1 levels during nerve repair. FAU - La Fleur, M AU - La Fleur M AD - Department of Anatomy, University of California, San Francisco 94143-0750, USA. FAU - Underwood, J L AU - Underwood JL FAU - Rappolee, D A AU - Rappolee DA FAU - Werb, Z AU - Werb Z LA - eng GR - T32 ES007106/ES/NIEHS NIH HHS/United States GR - T32ES07106/ES/NIEHS NIH HHS/United States GR - DE10306/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (Glycoproteins) RN - 0 (Interleukin-1) RN - 0 (RNA, Messenger) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 0 (Transforming Growth Factor beta) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.24.- (Collagenases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Basement Membrane/*physiology MH - Collagenases/*biosynthesis MH - Culture Media, Conditioned MH - Cytokines/*pharmacology MH - Female MH - Gene Expression Regulation, Enzymologic MH - Glycoproteins/*biosynthesis MH - Interleukin-1/pharmacology MH - Macrophages/*physiology MH - Matrix Metalloproteinase 3/*biosynthesis MH - Matrix Metalloproteinase 9 MH - Mice MH - Mice, Inbred Strains MH - *Nerve Regeneration MH - Neurons/drug effects/*physiology MH - Organ Culture Techniques MH - Polymerase Chain Reaction MH - RNA, Messenger/biosynthesis MH - Regeneration MH - Schwann Cells/physiology MH - Sciatic Nerve/injuries/*physiology MH - Tissue Inhibitor of Metalloproteinases MH - Transcription, Genetic MH - Transforming Growth Factor beta/pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology MH - *Wound Healing PMC - PMC2196375 EDAT- 1996/12/01 00:00 MHDA- 1996/12/01 00:01 PMCR- 1997/06/01 CRDT- 1996/12/01 00:00 PHST- 1996/12/01 00:00 [pubmed] PHST- 1996/12/01 00:01 [medline] PHST- 1996/12/01 00:00 [entrez] PHST- 1997/06/01 00:00 [pmc-release] AID - 10.1084/jem.184.6.2311 [doi] PST - ppublish SO - J Exp Med. 1996 Dec 1;184(6):2311-26. doi: 10.1084/jem.184.6.2311.