Cytokine Regulation of MMP-9 in Peripheral Glia: Implications for Pathological Processes and Pain in Injured Nerve

Overview

Journal Brain Behav Immun

Publisher Elsevier

Specialties Allergy & Immunology
Neurology
Psychiatry

Date 2006 Dec 27

PMID 17189680

Citations 62

Authors

Sharmila Chattopadhyay

Robert R Myers

Julie Janes

Veronica Shubayev

Affiliations

Soon will be listed here.

Abstract

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-alpha and IL-1beta 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.

Citing Articles

MMP9: Link between neuropathy and colorectal cancer?.

Regalado C, Balogh M Front Mol Biosci. 2024; 11:1451611.

PMID: 39664453 PMC: 11631744. DOI: 10.3389/fmolb.2024.1451611.

Sacral Bioneuromodulation: The Role of Bone Marrow Aspirate in Spinal Cord Injuries.

Lana J, Navani A, Jeyaraman M, Santos N, Pires L, Santos G Bioengineering (Basel). 2024; 11(5).

PMID: 38790327 PMC: 11118755. DOI: 10.3390/bioengineering11050461.

Brief Electrical Stimulation Promotes Recovery after Surgical Repair of Injured Peripheral Nerves.

Gordon T Int J Mol Sci. 2024; 25(1).

PMID: 38203836 PMC: 10779324. DOI: 10.3390/ijms25010665.

Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics.

Ciapala K, Mika J Pharmaceuticals (Basel). 2023; 16(11).

PMID: 38004489 PMC: 10675751. DOI: 10.3390/ph16111624.

Genome Wide Association Study of Neuropathic Ocular Pain.

Huang J, Rodriguez D, Slifer S, Martin E, Levitt R, Galor A Ophthalmol Sci. 2023; 4(2):100384.

PMID: 37868788 PMC: 10587615. DOI: 10.1016/j.xops.2023.100384.

References

Myers R, Campana W, Shubayev V . The role of neuroinflammation in neuropathic pain: mechanisms and therapeutic targets. Drug Discov Today. 2006; 11(1-2):8-20. DOI: 10.1016/S1359-6446(05)03637-8. View

Larsen P, Goncalves DaSilva A, Conant K, Yong V . Myelin formation during development of the CNS is delayed in matrix metalloproteinase-9 and -12 null mice. J Neurosci. 2006; 26(8):2207-14. PMC: 6674803. DOI: 10.1523/JNEUROSCI.1880-05.2006. View

Shubayev V, Angert M, Dolkas J, Campana W, Palenscar K, Myers R . TNFalpha-induced MMP-9 promotes macrophage recruitment into injured peripheral nerve. Mol Cell Neurosci. 2005; 31(3):407-15. PMC: 4431648. DOI: 10.1016/j.mcn.2005.10.011. View

DSouza C, Moscarello M . Differences in susceptibility of MBP charge isomers to digestion by stromelysin-1 (MMP-3) and release of an immunodominant epitope. Neurochem Res. 2006; 31(8):1045-54. DOI: 10.1007/s11064-006-9116-9. View

Hsu J, McKeon R, Goussev S, Werb Z, Lee J, Trivedi A . Matrix metalloproteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. J Neurosci. 2006; 26(39):9841-50. PMC: 2659718. DOI: 10.1523/JNEUROSCI.1993-06.2006. View

Liefner M, Siebert H, Sachse T, Michel U, Kollias G, Bruck W . The role of TNF-alpha during Wallerian degeneration. J Neuroimmunol. 2000; 108(1-2):147-52. DOI: 10.1016/s0165-5728(00)00262-9. View

Shubayev V, Myers R . Upregulation and interaction of TNFalpha and gelatinases A and B in painful peripheral nerve injury. Brain Res. 2000; 855(1):83-9. DOI: 10.1016/s0006-8993(99)02321-5. View

Vecil G, LARSEN P, Corley S, Herx L, Besson A, Goodyer C . Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo. J Neurosci Res. 2000; 61(2):212-24. DOI: 10.1002/1097-4547(20000715)61:2<212::AID-JNR12>3.0.CO;2-9. View

Ferguson T, Muir D . MMP-2 and MMP-9 increase the neurite-promoting potential of schwann cell basal laminae and are upregulated in degenerated nerve. Mol Cell Neurosci. 2000; 16(2):157-67. DOI: 10.1006/mcne.2000.0859. View

10.

Genersch E, Hayess K, Neuenfeld Y, Haller H . Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and -independent pathways. J Cell Sci. 2000; 113 Pt 23:4319-30. DOI: 10.1242/jcs.113.23.4319. View

11.

Siebert H, Dippel N, Mader M, Weber F, Bruck W . Matrix metalloproteinase expression and inhibition after sciatic nerve axotomy. J Neuropathol Exp Neurol. 2001; 60(1):85-93. DOI: 10.1093/jnen/60.1.85. View

12.

Asahi M, Wang X, Mori T, Sumii T, Jung J, Moskowitz M . Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. J Neurosci. 2001; 21(19):7724-32. PMC: 6762894. View

13.

Paulson P, Casey K, Morrow T . Long-term changes in behavior and regional cerebral blood flow associated with painful peripheral mononeuropathy in the rat. Pain. 2002; 95(1-2):31-40. PMC: 1828034. DOI: 10.1016/s0304-3959(01)00370-0. View

14.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

15.

Stoll G, Jander S, Myers R . Degeneration and regeneration of the peripheral nervous system: from Augustus Waller's observations to neuroinflammation. J Peripher Nerv Syst. 2002; 7(1):13-27. DOI: 10.1046/j.1529-8027.2002.02002.x. View

16.

Shubayev V, Myers R . Endoneurial remodeling by TNFalph- and TNFalpha-releasing proteases. A spatial and temporal co-localization study in painful neuropathy. J Peripher Nerv Syst. 2002; 7(1):28-36. DOI: 10.1046/j.1529-8027.2002.02003.x. View

17.

Hughes P, Wells G, Perry V, Brown M, Miller K . Comparison of matrix metalloproteinase expression during Wallerian degeneration in the central and peripheral nervous systems. Neuroscience. 2002; 113(2):273-87. DOI: 10.1016/s0306-4522(02)00183-5. View

18.

Rosenberg G . Matrix metalloproteinases in neuroinflammation. Glia. 2002; 39(3):279-91. DOI: 10.1002/glia.10108. View

19.

Pfaffl M . A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001; 29(9):e45. PMC: 55695. DOI: 10.1093/nar/29.9.e45. View

20.

Renaud S, Erne B, Fuhr P, Said G, Lacroix C, Steck A . Matrix metalloproteinases-9 and -2 in secondary vasculitic neuropathies. Acta Neuropathol. 2002; 105(1):37-42. DOI: 10.1007/s00401-002-0607-8. View