Effect of astrocyte-targeted production of IL-6 on traumatic brain injury and its impact on the cortical transcriptome

TY - JOUR

T1 - Effect of astrocyte-targeted production of IL-6 on traumatic brain injury and its impact on the cortical transcriptome

AU - Quintana, Albert

AU - Molinero, Amalia

AU - Borup, Rehannah

AU - Nielsen, Finn Cilius

AU - Campbell, Iain L

AU - Penkowa, Milena

AU - Hidalgo, Juan

N1 - Keywords: Animals; Apoptosis; Astrocytes; Brain Injuries; Cell Movement; Cell Proliferation; Encephalitis; Gene Expression Profiling; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hemostasis; Interleukin-6; Male; Mice; Mice, Knockout; Recombinant Fusion Proteins; Signal Transduction; Synaptic Transmission; Up-Regulation

PY - 2008

Y1 - 2008

N2 - Interleukin-6 (IL-6) is one of the key players in the response of the brain cortex to injury. We have described previously that astrocyte-driven production of IL-6 (GFAP-IL6) in transgenic mice, although causing spontaneous neuroinflammation and long term damage, is beneficial after an acute (freeze) injury in the cortex, increasing healing and decreasing oxidative stress and apoptosis. To determine the transcriptional basis for these responses here we analyzed the global gene expression profile of the cortex, at 0 (unlesioned), 1 or 4 days post lesion (dpl), in both GFAP-IL6 mice and their control littermates. GFAP-IL6 mice showed an increase in genes associated with the inflammatory response both at 1 dpl (Iftm1, Endod1) and 4 dpl (Gfap, C4b), decreased expression of proapoptotic genes (i.e. Gadd45b, Clic4, p21) as well as reduced expression of genes involved in the control of oxidative stress (Atf4). Furthermore, the presence of IL-6 altered the expression of genes involved in hemostasis (Vwf), cell migration and proliferation (Cap2), and synaptic activity (Vamp2). All these changes in gene expression could underlie the phenotype of the GFAP-IL6 mice after injury, but many other possible factors were also identified in this study, highlighting the utility of this approach for deciphering new pathways orchestrated by IL-6.

AB - Interleukin-6 (IL-6) is one of the key players in the response of the brain cortex to injury. We have described previously that astrocyte-driven production of IL-6 (GFAP-IL6) in transgenic mice, although causing spontaneous neuroinflammation and long term damage, is beneficial after an acute (freeze) injury in the cortex, increasing healing and decreasing oxidative stress and apoptosis. To determine the transcriptional basis for these responses here we analyzed the global gene expression profile of the cortex, at 0 (unlesioned), 1 or 4 days post lesion (dpl), in both GFAP-IL6 mice and their control littermates. GFAP-IL6 mice showed an increase in genes associated with the inflammatory response both at 1 dpl (Iftm1, Endod1) and 4 dpl (Gfap, C4b), decreased expression of proapoptotic genes (i.e. Gadd45b, Clic4, p21) as well as reduced expression of genes involved in the control of oxidative stress (Atf4). Furthermore, the presence of IL-6 altered the expression of genes involved in hemostasis (Vwf), cell migration and proliferation (Cap2), and synaptic activity (Vamp2). All these changes in gene expression could underlie the phenotype of the GFAP-IL6 mice after injury, but many other possible factors were also identified in this study, highlighting the utility of this approach for deciphering new pathways orchestrated by IL-6.

U2 - 10.1002/dneu.20584

DO - 10.1002/dneu.20584

M3 - Journal article

C2 - 18000830

SN - 1932-8451

VL - 68

SP - 195

EP - 208

JO - Developmental Neurobiology

JF - Developmental Neurobiology

IS - 2

ER -