Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy

Leppert, David; Hughes, P.; Huber, Steven J.; Erne, Beat; Grygar, Caroline; Said, G.; Miller, Karen; Steck, Andreas; Probst, A.; Fuhr, Peter

doi:10.1212/wnl.53.1.62

Cited by 91 publications

(59 citation statements)

References 39 publications

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“…TAPI inhibits TNF-α activation by chelating TNF-α converting enzyme (TACE) and, at higher doses, MMP-9 and other MMPs. MMP inhibition also improves electrophysiologic nerve conduction and motor performance (Leppert et al, 1999;Hsu et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In the nervous system, MMPs produce neuroinflammation by controlling neurovascular permeability, immune cell recruitment, demyelination, cell necrosis, and apoptosis (Yong et al, 1998;Kieseier et al, 1999b, Rosenberg, 2002Lee et al, 2004a, Yong, 2005. MMP-9 is upregulated in experimental peripheral neuropathy models (La Fleur et al, 1996;Kherif et al, 1998;Ferguson and Muir, 2000;Siebert et al, 2001;Hughes et al, 2002;Platt et al, 2003;Demestre et al, 2004) and in patients with symptomatic neuropathy (Leppert et al, 1999;Mawrin et al, 2003;Renaud et al, 2003;Gurer et al, 2004). We have recently shown that MMP-9 gene deletion or pharmacologic inhibition reduces injury-induced macrophage recruitment and protects nerves from axonal degeneration .…”

Section: Introductionmentioning

confidence: 99%

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Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve

Chattopadhyay

Myers

Janes

et al. 2007

Brain, Behavior, and Immunity

122

117

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Matrix metalloproteinase-9 (MMP-9) is an extracellular protease that is induced in Schwann cells hours after peripheral nerve injury and controls axonal degeneration and macrophage recruitment to the lesion. Here, we report a robust (90-fold) increase in MMP-9 mRNA within 24 h after rat sciatic nerve crush (1 to 60 days time-course). Using direct injection into a normal sciatic nerve, we identify the proinflammatory cytokines TNF-α and IL-1β as potent regulators of MMP-9 expression (Taqman qPCR, zymography). Myelinating Schwann cells produced MMP-9 in response to cytokine injection and crush nerve injury. MMP-9 gene deletion reduced unstimulated neuropathic nociceptive behavior after one week post-crush and preserved myelin thickness by protecting myelin basic protein (MBP) from degradation, tested by Western blot and immunofluorescence. These data suggest that MMP-9 expression in peripheral nerve is controlled by key proinflammatory cytokine pathways, and that its removal protects nerve fibers from demyelination and reduces neuropathic pain after injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve

Chattopadhyay

Myers

Janes

et al. 2007

Brain, Behavior, and Immunity

122

117

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“…Furthermore, macrophages in the TrJ nerve maintain a close spatial relationship with myelinated nerve axons. Though it is known that macrophages contribute to peripheral nerve demyelination in both P0 and connexin-32 peripheral neuropathies (Schmid et al 2000;Carenini et al 2001;Kobsar et al 2002), and likely do so in the TrJ neuropathy, it is not fully clear if MMPs directly participate in myelin degradation (Leppert et al 1999). Nonetheless, both MMP-2 and MMP-9 may degrade myelin basic protein, a prominent constituent of peripheral nerve myelin (Chandler et al 1995), and an undetermined MMP activity degrades P0 (Cammer et al 1981).…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase mediated degradation of basement membrane proteins in Trembler J neuropathy nerves

Misko

Ferguson

Notterpek

2002

Journal of Neurochemistry

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A single point mutation in peripheral myelin protein 22 (pmp22) of the Trembler-J (TrJ) mouse models the human peripheral neuropathy, Charcot-Marie-Tooth disease type 1 A (CMT1A). An unexplored aspect of this disease is the gradual remodeling of the extracellular matrix in affected nerves. To elucidate the mechanism responsible for these changes, the levels of the extracellular matrix molecules laminin, collagen IV, and fibronectin were determined. In TrJ nerves, laminin is modestly increased while full-length forms of collagen IV and fibronectin are decreased. Matrix metalloproteinases (MMPs) are known to degrade multiple matrix molecules; therefore, nerves were assayed for MMP-2 and MMP-9 proteins. In neuropathy nerves, elevated levels of MMP-2 and MMP-9 were detected on western blots, and gelatin zymography confirmed the up-regulation of gelatinalytic activity in affected samples. Immunostaining studies revealed an increase in the numbers of MMP-2-and MMP-9-expressing cells in TrJ nerves. Cell type-specific immunolabeling showed that infiltrating macrophages are a significant source of both MMP-2 and MMP-9. Finally, the degradation of exogenous collagen IV by TrJ nerve lysates was prevented with a specific MMP inhibitor. Together these observations suggest that infiltration by MMP-expressing macrophages contributes to the remodeling of the TrJ nerve matrix.

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“…In another animal model, experimental allergic neuritis, which is a model for the Guillain-Barré syndrome, there was expression of MMPs. Treatment with an inhibitor of MMPs improved electrophysiologic nerve conduction and motor performance (Redford et al, 1997;Hughes et al, 1998;Leppert et al, 1999).…”

Section: Mmps In Neuroinflammation In the Absence Of Hypoxiamentioning

confidence: 99%

Matrix metalloproteinases in neuroinflammation

Rosenberg

2002

Glia

778

667

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Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases. Brain cells express both constitutive and inducible MMPs in response to cellular stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as inactive enzymes, the MMPs require activation by other proteases and free radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which includes the recently discovered ADAMs (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families. MPs have complex roles at the cell surface and within the extracellular matrix. At the cell surface, they act as sheddases, releasing growth factors, death receptors, and death-inducing ligands, making them important in cell survival and death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the MMPs. Synthetic inhibitors have been developed for the treatment of arthritis and cancer. These hydroxymate-based compounds have been shown to reduce injury in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), cerebral ischemia, intracerebral hemorrhage, and viral and bacterial infections. MPs have both beneficial and detrimental roles; understanding their expression in various CNS insults will allow for the use of MMP inhibitors in the treatment of neurological disorders. GLIA 39: 279 -291, 2002.

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Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy

Cited by 91 publications

References 39 publications

Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve

Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve

Matrix metalloproteinase mediated degradation of basement membrane proteins in Trembler J neuropathy nerves

Matrix metalloproteinases in neuroinflammation

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