A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation

Eric J Downer; Thelma R Cowley; Fionnuala Cox; Francis O Maher; Vladimir Berezin; Elisabeth Bock; Marina A Lynch

doi:10.1111/j.1471-4159.2009.06076.x

A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation

Eric J Downer, Thelma R Cowley, Fionnuala Cox, Francis O Maher, Vladimir Berezin, Elisabeth Bock, Marina A Lynch

Institut for Neurovidenskab

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

39 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Jun

Originalsprog	Engelsk
Tidsskrift	Journal of Neurochemistry
Vol/bind	109
Udgave nummer	5
Sider (fra-til)	1516-25
Antal sider	9
ISSN	0022-3042
DOI	https://doi.org/10.1111/j.1471-4159.2009.06076.x
Status	Udgivet - 2009

Bibliografisk note

Keywords: Age Factors; Animals; Animals, Newborn; Anti-Inflammatory Agents; Antigens, CD; Antigens, CD40; Cells, Cultured; Cerebral Cortex; Gene Expression Regulation; Hippocampus; Insulin-Like Growth Factor I; Interferon-gamma; Male; Neural Cell Adhesion Molecules; Neuroglia; Neurons; Oncogene Protein v-akt; Rats; Rats, Wistar

Adgang til dokumentet

10.1111/j.1471-4159.2009.06076.x

Citationsformater

@article{cbfa6dd0b1b811df825b000ea68e967b,

title = "A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation",

abstract = "Microglial cell activity increases in the rat hippocampus during normal brain aging. The neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as an anti-inflammatory agent in the hippocampus of the aged rat, promoting CD200 ligand expression while attenuating glial cell activation and subsequent pro-inflammatory cytokine production. The aim of the current study was to determine if FGL corrects the age-related imbalance in hippocampal levels of insulin-like growth factor-1 (IGF-1) and pro-inflammatory interferon-gamma (IFNgamma), and subsequently attenuates the glial reactivity associated with aging. Administration of FGL reversed the age-related decline in IGF-1 in hippocampus, while abrogating the age-related increase in IFNgamma. FGL robustly promotes IGF-1 release from primary neurons and IGF-1 is pivotal in FGL induction of neuronal Akt phosphorylation and subsequent CD200 ligand expression in vitro. In addition, FGL abrogates both age- and IFNgamma-induced increases in markers of glial cell activation, including major histocompatibility complex class II (MHCII) and CD40. Finally, the proclivity of FGL to attenuate IFNgamma-induced glial cell activation in vitro is IGF-1-dependent. Overall, these findings suggest that FGL, by correcting the age-related imbalance in hippocampal levels of IGF-1 and IFNgamma, attenuates glial cell activation associated with aging. These findings also highlight a novel mechanism by which FGL can impact on neuronal CD200 ligand expression and subsequently on glial cell activation status.",

author = "Downer, {Eric J} and Cowley, {Thelma R} and Fionnuala Cox and Maher, {Francis O} and Vladimir Berezin and Elisabeth Bock and Lynch, {Marina A}",

note = "Keywords: Age Factors; Animals; Animals, Newborn; Anti-Inflammatory Agents; Antigens, CD; Antigens, CD40; Cells, Cultured; Cerebral Cortex; Gene Expression Regulation; Hippocampus; Insulin-Like Growth Factor I; Interferon-gamma; Male; Neural Cell Adhesion Molecules; Neuroglia; Neurons; Oncogene Protein v-akt; Rats; Rats, Wistar",

year = "2009",

doi = "10.1111/j.1471-4159.2009.06076.x",

language = "English",

volume = "109",

pages = "1516--25",

journal = "Journal of Neurochemistry",

issn = "0022-3042",

publisher = "Wiley-Blackwell",

number = "5",

}

TY - JOUR

T1 - A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation

AU - Downer, Eric J

AU - Cowley, Thelma R

AU - Cox, Fionnuala

AU - Maher, Francis O

AU - Berezin, Vladimir

AU - Bock, Elisabeth

AU - Lynch, Marina A

N1 - Keywords: Age Factors; Animals; Animals, Newborn; Anti-Inflammatory Agents; Antigens, CD; Antigens, CD40; Cells, Cultured; Cerebral Cortex; Gene Expression Regulation; Hippocampus; Insulin-Like Growth Factor I; Interferon-gamma; Male; Neural Cell Adhesion Molecules; Neuroglia; Neurons; Oncogene Protein v-akt; Rats; Rats, Wistar

PY - 2009

Y1 - 2009

N2 - Microglial cell activity increases in the rat hippocampus during normal brain aging. The neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as an anti-inflammatory agent in the hippocampus of the aged rat, promoting CD200 ligand expression while attenuating glial cell activation and subsequent pro-inflammatory cytokine production. The aim of the current study was to determine if FGL corrects the age-related imbalance in hippocampal levels of insulin-like growth factor-1 (IGF-1) and pro-inflammatory interferon-gamma (IFNgamma), and subsequently attenuates the glial reactivity associated with aging. Administration of FGL reversed the age-related decline in IGF-1 in hippocampus, while abrogating the age-related increase in IFNgamma. FGL robustly promotes IGF-1 release from primary neurons and IGF-1 is pivotal in FGL induction of neuronal Akt phosphorylation and subsequent CD200 ligand expression in vitro. In addition, FGL abrogates both age- and IFNgamma-induced increases in markers of glial cell activation, including major histocompatibility complex class II (MHCII) and CD40. Finally, the proclivity of FGL to attenuate IFNgamma-induced glial cell activation in vitro is IGF-1-dependent. Overall, these findings suggest that FGL, by correcting the age-related imbalance in hippocampal levels of IGF-1 and IFNgamma, attenuates glial cell activation associated with aging. These findings also highlight a novel mechanism by which FGL can impact on neuronal CD200 ligand expression and subsequently on glial cell activation status.

AB - Microglial cell activity increases in the rat hippocampus during normal brain aging. The neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as an anti-inflammatory agent in the hippocampus of the aged rat, promoting CD200 ligand expression while attenuating glial cell activation and subsequent pro-inflammatory cytokine production. The aim of the current study was to determine if FGL corrects the age-related imbalance in hippocampal levels of insulin-like growth factor-1 (IGF-1) and pro-inflammatory interferon-gamma (IFNgamma), and subsequently attenuates the glial reactivity associated with aging. Administration of FGL reversed the age-related decline in IGF-1 in hippocampus, while abrogating the age-related increase in IFNgamma. FGL robustly promotes IGF-1 release from primary neurons and IGF-1 is pivotal in FGL induction of neuronal Akt phosphorylation and subsequent CD200 ligand expression in vitro. In addition, FGL abrogates both age- and IFNgamma-induced increases in markers of glial cell activation, including major histocompatibility complex class II (MHCII) and CD40. Finally, the proclivity of FGL to attenuate IFNgamma-induced glial cell activation in vitro is IGF-1-dependent. Overall, these findings suggest that FGL, by correcting the age-related imbalance in hippocampal levels of IGF-1 and IFNgamma, attenuates glial cell activation associated with aging. These findings also highlight a novel mechanism by which FGL can impact on neuronal CD200 ligand expression and subsequently on glial cell activation status.

U2 - 10.1111/j.1471-4159.2009.06076.x

DO - 10.1111/j.1471-4159.2009.06076.x

M3 - Journal article

C2 - 19457161

SN - 0022-3042

VL - 109

SP - 1516

EP - 1525

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

IS - 5

ER -