Abstract
In the central nervous system (CNS), the transcription factor nuclear factor (NF)-κB is a key regulator of inflammation and secondary injury processes. After trauma or disease, the expression of NF-κB-dependent genes is highly activated, leading to both protective and detrimental effects on CNS recovery. We demonstrate that selective inactivation of astroglial NF-κB in transgenic mice expressing a dominant negative (dn) form of the inhibitor of κBα under the control of an astrocyte-specific promoter (glial fibrillary acidic protein [GFAP]-dn mice) leads to a dramatic improvement in functional recovery 8 wk after contusive spinal cord injury (SCI). Histologically, GFAP mice exhibit reduced lesion volume and substantially increased white matter preservation. In parallel, they show reduced expression of proinflammatory chemokines and cytokines, such as CXCL10, CCL2, and transforming growth factor-β2, and of chondroitin sulfate proteoglycans participating in the formation of the glial scar. We conclude that selective inhibition of NF-κB signaling in astrocytes results in protective effects after SCI and propose the NF-κB pathway as a possible new target for the development of therapeutic strategies for the treatment of SCI. JEM
| Original language | English |
|---|---|
| Pages (from-to) | 145-156 |
| Number of pages | 12 |
| Journal | Journal of Experimental Medicine |
| Volume | 202 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 4 2005 |
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ASJC Scopus subject areas
- Immunology
Cite this
Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury. / Brambilla, Roberta; Bracchi-Ricard, Valerie; Hu, Wen Hui; Frydel, Beata; Bramwell, Annmarie; Karmally, Shaffiat; Green, Edward J.; Bethea, John R.
In: Journal of Experimental Medicine, Vol. 202, No. 1, 04.07.2005, p. 145-156.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury
AU - Brambilla, Roberta
AU - Bracchi-Ricard, Valerie
AU - Hu, Wen Hui
AU - Frydel, Beata
AU - Bramwell, Annmarie
AU - Karmally, Shaffiat
AU - Green, Edward J.
AU - Bethea, John R.
PY - 2005/7/4
Y1 - 2005/7/4
N2 - In the central nervous system (CNS), the transcription factor nuclear factor (NF)-κB is a key regulator of inflammation and secondary injury processes. After trauma or disease, the expression of NF-κB-dependent genes is highly activated, leading to both protective and detrimental effects on CNS recovery. We demonstrate that selective inactivation of astroglial NF-κB in transgenic mice expressing a dominant negative (dn) form of the inhibitor of κBα under the control of an astrocyte-specific promoter (glial fibrillary acidic protein [GFAP]-dn mice) leads to a dramatic improvement in functional recovery 8 wk after contusive spinal cord injury (SCI). Histologically, GFAP mice exhibit reduced lesion volume and substantially increased white matter preservation. In parallel, they show reduced expression of proinflammatory chemokines and cytokines, such as CXCL10, CCL2, and transforming growth factor-β2, and of chondroitin sulfate proteoglycans participating in the formation of the glial scar. We conclude that selective inhibition of NF-κB signaling in astrocytes results in protective effects after SCI and propose the NF-κB pathway as a possible new target for the development of therapeutic strategies for the treatment of SCI. JEM
AB - In the central nervous system (CNS), the transcription factor nuclear factor (NF)-κB is a key regulator of inflammation and secondary injury processes. After trauma or disease, the expression of NF-κB-dependent genes is highly activated, leading to both protective and detrimental effects on CNS recovery. We demonstrate that selective inactivation of astroglial NF-κB in transgenic mice expressing a dominant negative (dn) form of the inhibitor of κBα under the control of an astrocyte-specific promoter (glial fibrillary acidic protein [GFAP]-dn mice) leads to a dramatic improvement in functional recovery 8 wk after contusive spinal cord injury (SCI). Histologically, GFAP mice exhibit reduced lesion volume and substantially increased white matter preservation. In parallel, they show reduced expression of proinflammatory chemokines and cytokines, such as CXCL10, CCL2, and transforming growth factor-β2, and of chondroitin sulfate proteoglycans participating in the formation of the glial scar. We conclude that selective inhibition of NF-κB signaling in astrocytes results in protective effects after SCI and propose the NF-κB pathway as a possible new target for the development of therapeutic strategies for the treatment of SCI. JEM
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UR - http://www.scopus.com/inward/citedby.url?scp=22344431751&partnerID=8YFLogxK
U2 - 10.1084/jem.20041918
DO - 10.1084/jem.20041918
M3 - Article
C2 - 15998793
AN - SCOPUS:22344431751
VL - 202
SP - 145
EP - 156
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 1
ER -