TNF superfamily member TWEAK exacerbates inflammation and demyelination in the cuprizone-induced model.
Inflammatory cytokines have been implicated in the pathology of multiple neurologic diseases, including multiple sclerosis. We examined the role of the TNF family member TWEAK in neuroinflammation. Cuprizone-fed mice undergo neuroinflammation and demyelination in the brain, but upon removal of cuprizone from the diet, inflammation is resolved and remyelination occurs. Using this model, we demonstrate that mice lacking TWEAK exhibit a significant delay in demyelination and microglial infiltration. During remyelination, mice lacking the TWEAK gene demonstrate only a marginal delay in remyelination. Thus, this study identifies a primary role of TWEAK in promoting neuroinflammation and exacerbating demyelination during cuprizone-induced damage.
Iocca
Heather A
HA
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599-7295, United States.
Plant
Sheila R
SR
Wang
Ying
Y
Runkel
Laura
L
O'Connor
Brian P
BP
Lundsmith
Emma T
ET
Hahm
Kyungmin
K
van Deventer
Hendrik W
HW
Burkly
Linda C
LC
Ting
Jenny P-Y
JP
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002614:Chelating Agents / Q000633:toxicity; D003300:Copper; D003471:Cuprizone / Q000633:toxicity; D000074049:Cytokine TWEAK; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000503:physiopathology*; D004311:Double-Blind Method; D004660:Encephalitis / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000502:physiology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D002614:Chelating Agents; D000074049:Cytokine TWEAK; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D000074050:TWEAK Receptor; C491645:Tnfsf12 protein, mouse; D048069:Tumor Necrosis Factors; D003471:Cuprizone; D003300:Copper