A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL.
Age-related cognitive deficits in hippocampus are correlated with neuroinflammatory changes, typified by increased pro-inflammatory cytokine production and microglial activation. We provide evidence that the neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as a novel anti-inflammatory agent. Administration of FGL to aged rats attenuated the increased expression of markers of activated microglia, the increase in pro-inflammatory interleukin-1beta (IL-1beta) and the impairment in long-term potentiation (LTP). We report that the age-related increase in microglial activation was accompanied by decreased expression of neuronal CD200, and suggest that the proclivity of FGL to suppress microglial activation is due to its stimulatory effect on neuronal CD200. We demonstrate that FGL enhanced interleukin-4 (IL-4) release from glial cells and IL-4 in turn enhanced neuronal CD200 in vitro. We provide evidence that the increase in CD200 is reliant on IL-4-induced extracellular signal-regulated kinase (ERK) signal transduction. These findings provide the first evidence of a role for FGL as an anti-inflammatory agent and identify a mechanism by which FGL controls microglial activation.
Downer
Eric J
EJ
Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland.
Cowley
Thelma R
TR
Lyons
Anthony
A
Mills
Kingston H G
KH
Berezin
Vladimir
V
Bock
Elisabeth
E
Lynch
Marina A
MA
D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005911:Gliosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D015703:Antigens, CD; D053583:Interleukin-1beta; C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules; D015847:Interleukin-4; C042739:antigens, CD200