Role for nerve growth factor in the in vivo regulation of glutathione in response to LPS in mice
- Journal Article
Since the redox state regulator glutathione (GSH) influences lipopolysaccharide (LPS) anorexia, we studied the roles of tumour necrosis factor-alpha (TNFα) and nerve growth factor (NGF) in the GSH response to intraperitoneal (ip) LPS injection in mice. Basal NGF and GSH levels were up-regulated in brain and liver of TNFα-knock-out (KO) mice, and this was associated with attenuated LPS anorexia. The increases in NGF and GSH presumably contributed to the attenuated anorexia in response to LPS because transgenic mice over-expressing NGF (NGF-tg) also had increased GSH levels and displayed attenuated anorexia compared to the corresponding wild type (WT) mice. Attenuated LPS anorexia in NGF-tg mice was accompanied by reduced serum TNFα and IFNγ levels compared to WT mice. In response to a second injection of LPS, NGF and GSH levels, but not TNFα levels changed. This suggests that in vivo tissue GSH changes following LPS in LPS-naïve or LPS-pretreated mice are regulated by NGF rather than TNFα. The finding that genetic TNFα deficiency did not inhibit the acute GSH response to LPS supports this interpretation. In sum, the results indicate i) that a decrease or increase in NGF is accompanied by a decrease or increase in GSH levels and ii) that elevated NGF and/or GSH levels attenuate some of the responses to LPS such as anorexia and cytokine production. Show more
Journal / seriesEuropean cytokine network
Pages / Article No.
Subjectreactive oxygen species; cytokine; food intake; liver; brain; mitochondria
Organisational unit03274 - Langhans, Wolfgang (emeritus)
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