Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo

Giacomo G. Vecil, Peter H. Larsen, Shannon M. Corley, Leonie M. Herx, Arnaud Besson, Cynthia G. Goodyer, V. Wee Yong

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

An acute trauma to the CNS rapidly results in the upregulation of inflammatory cytokines that include interleukin-1 (IL-1). We report here that the levels of several matrix metalloproteinases (MMPs) are also elevated following a corticectomy trauma injury to the mouse CNS. The delayed upregulation of MMPs compared to that for IL-1 suggests the possibility that inflammatory cytokines regulate MMP production in CNS trauma. To resolve this, we developed a method to isolate and maintain highly enriched human fetal neurons or astrocytes in culture and examined the regulation by cytokines of the activity of a subgroup of MMPs, the gelatinases (MMP-2 and - 9). While both neuronal and astrocytic cultures displayed comparable MMP-2 activity, as evidenced by gelatin zymography, levels of MMP-9 were proportionately higher in neurons compared to astrocytes. Of a variety of cytokines and growth factors tested in vitro, only IL-1β was effective in increasing the neuronal expression of MMP-9. Finally, an IL-1 receptor antagonist attenuated the increase of neuronal MMP-9 in culture and abolished the injury-induced increase of MMP-9 in the mouse brain. These results implicate IL-1β as a key regulator of neuronal MMP-9 in culture and of the elevation of MMP-9 that occurs following mouse CNS traumal. (C) 2000 Wiley- Liss, Inc.

Original languageEnglish (US)
Pages (from-to)212-224
Number of pages13
JournalJournal of Neuroscience Research
Volume61
Issue number2
DOIs
StatePublished - Jul 15 2000
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 9
Interleukin-1
Neurons
Matrix Metalloproteinases
Cytokines
Wounds and Injuries
Matrix Metalloproteinase 2
Astrocytes
Up-Regulation
Gelatinases
Interleukin-1 Receptors
Gelatin
Traumatic Brain Injury
Intercellular Signaling Peptides and Proteins
Brain

Keywords

  • CNS trauma
  • Cytokines
  • Human neurons
  • MMP

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo. / Vecil, Giacomo G.; Larsen, Peter H.; Corley, Shannon M.; Herx, Leonie M.; Besson, Arnaud; Goodyer, Cynthia G.; Yong, V. Wee.

In: Journal of Neuroscience Research, Vol. 61, No. 2, 15.07.2000, p. 212-224.

Research output: Contribution to journalArticle

Vecil, Giacomo G. ; Larsen, Peter H. ; Corley, Shannon M. ; Herx, Leonie M. ; Besson, Arnaud ; Goodyer, Cynthia G. ; Yong, V. Wee. / Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo. In: Journal of Neuroscience Research. 2000 ; Vol. 61, No. 2. pp. 212-224.
@article{fb290b27ebe94789907d7457f8462c83,
title = "Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo",
abstract = "An acute trauma to the CNS rapidly results in the upregulation of inflammatory cytokines that include interleukin-1 (IL-1). We report here that the levels of several matrix metalloproteinases (MMPs) are also elevated following a corticectomy trauma injury to the mouse CNS. The delayed upregulation of MMPs compared to that for IL-1 suggests the possibility that inflammatory cytokines regulate MMP production in CNS trauma. To resolve this, we developed a method to isolate and maintain highly enriched human fetal neurons or astrocytes in culture and examined the regulation by cytokines of the activity of a subgroup of MMPs, the gelatinases (MMP-2 and - 9). While both neuronal and astrocytic cultures displayed comparable MMP-2 activity, as evidenced by gelatin zymography, levels of MMP-9 were proportionately higher in neurons compared to astrocytes. Of a variety of cytokines and growth factors tested in vitro, only IL-1β was effective in increasing the neuronal expression of MMP-9. Finally, an IL-1 receptor antagonist attenuated the increase of neuronal MMP-9 in culture and abolished the injury-induced increase of MMP-9 in the mouse brain. These results implicate IL-1β as a key regulator of neuronal MMP-9 in culture and of the elevation of MMP-9 that occurs following mouse CNS traumal. (C) 2000 Wiley- Liss, Inc.",
keywords = "CNS trauma, Cytokines, Human neurons, MMP",
author = "Vecil, {Giacomo G.} and Larsen, {Peter H.} and Corley, {Shannon M.} and Herx, {Leonie M.} and Arnaud Besson and Goodyer, {Cynthia G.} and Yong, {V. Wee}",
year = "2000",
month = "7",
day = "15",
doi = "10.1002/1097-4547(20000715)61:2<212::AID-JNR12>3.0.CO;2-9",
language = "English (US)",
volume = "61",
pages = "212--224",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo

AU - Vecil, Giacomo G.

AU - Larsen, Peter H.

AU - Corley, Shannon M.

AU - Herx, Leonie M.

AU - Besson, Arnaud

AU - Goodyer, Cynthia G.

AU - Yong, V. Wee

PY - 2000/7/15

Y1 - 2000/7/15

N2 - An acute trauma to the CNS rapidly results in the upregulation of inflammatory cytokines that include interleukin-1 (IL-1). We report here that the levels of several matrix metalloproteinases (MMPs) are also elevated following a corticectomy trauma injury to the mouse CNS. The delayed upregulation of MMPs compared to that for IL-1 suggests the possibility that inflammatory cytokines regulate MMP production in CNS trauma. To resolve this, we developed a method to isolate and maintain highly enriched human fetal neurons or astrocytes in culture and examined the regulation by cytokines of the activity of a subgroup of MMPs, the gelatinases (MMP-2 and - 9). While both neuronal and astrocytic cultures displayed comparable MMP-2 activity, as evidenced by gelatin zymography, levels of MMP-9 were proportionately higher in neurons compared to astrocytes. Of a variety of cytokines and growth factors tested in vitro, only IL-1β was effective in increasing the neuronal expression of MMP-9. Finally, an IL-1 receptor antagonist attenuated the increase of neuronal MMP-9 in culture and abolished the injury-induced increase of MMP-9 in the mouse brain. These results implicate IL-1β as a key regulator of neuronal MMP-9 in culture and of the elevation of MMP-9 that occurs following mouse CNS traumal. (C) 2000 Wiley- Liss, Inc.

AB - An acute trauma to the CNS rapidly results in the upregulation of inflammatory cytokines that include interleukin-1 (IL-1). We report here that the levels of several matrix metalloproteinases (MMPs) are also elevated following a corticectomy trauma injury to the mouse CNS. The delayed upregulation of MMPs compared to that for IL-1 suggests the possibility that inflammatory cytokines regulate MMP production in CNS trauma. To resolve this, we developed a method to isolate and maintain highly enriched human fetal neurons or astrocytes in culture and examined the regulation by cytokines of the activity of a subgroup of MMPs, the gelatinases (MMP-2 and - 9). While both neuronal and astrocytic cultures displayed comparable MMP-2 activity, as evidenced by gelatin zymography, levels of MMP-9 were proportionately higher in neurons compared to astrocytes. Of a variety of cytokines and growth factors tested in vitro, only IL-1β was effective in increasing the neuronal expression of MMP-9. Finally, an IL-1 receptor antagonist attenuated the increase of neuronal MMP-9 in culture and abolished the injury-induced increase of MMP-9 in the mouse brain. These results implicate IL-1β as a key regulator of neuronal MMP-9 in culture and of the elevation of MMP-9 that occurs following mouse CNS traumal. (C) 2000 Wiley- Liss, Inc.

KW - CNS trauma

KW - Cytokines

KW - Human neurons

KW - MMP

UR - http://www.scopus.com/inward/record.url?scp=0034662085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034662085&partnerID=8YFLogxK

U2 - 10.1002/1097-4547(20000715)61:2<212::AID-JNR12>3.0.CO;2-9

DO - 10.1002/1097-4547(20000715)61:2<212::AID-JNR12>3.0.CO;2-9

M3 - Article

C2 - 10878594

AN - SCOPUS:0034662085

VL - 61

SP - 212

EP - 224

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 2

ER -