Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration

Autor: Karine Palin, Colm Cunningham, Penny Forse, V. Hugh Perry, Nick Platt
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: Neurobiology of Disease, Vol 30, Iss 1, Pp 19-29 (2008)
Druh dokumentu: article
ISSN: 1095-953X
83619410
DOI: 10.1016/j.nbd.2007.11.012
Popis: Axon loss in the CNS is characteristic of many neurodegenerative diseases but the mechanisms of axon degeneration are poorly understood. In particular, we know little of the inflammatory response triggered by CNS axon degeneration with comparison to that provoked by death of the neuronal cell body. We show that Wallerian degeneration of the mouse optic nerve induces transcription of TGF-β1 and TNF-α, but not pro-inflammatory cytokines IL-1β and IL-6 and microglial activation. This atypical inflammatory response resembles macrophages that have phagocytosed apoptotic cells and prion-infected CNS. Significantly, peripheral endotoxin challenge after injury switched this profile by inducing IL-1β, IL-6 transcripts, other inflammation-associated products and reducing neurofilament immunoreactivity. We propose that microglia are activated by Wallerian degeneration and persist in an atypical but “primed” state and can be switched by systemic inflammation to provoke a classical pro-inflammatory profile with potentially deleterious consequences.
Databáze: Directory of Open Access Journals
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