Differential induction of adrenomedullin, interleukins and tumour necrosis factor‐αby lipopolysaccharide in rat tissues in vivo

1. The aim of the present study was to determine the temporal changes in tissue adrenomedullin (AM) and cytokine contents and cytokine and preproAM mRNA levels in the kidney, liver, adrenal gland and spleen of lipopolysaccharide (LPS)-treated rats. 2. Rats were injected with LPS (10 mg/kg, i.p.). Radioimmunoassay and solution hybridization-RNase protection assays were used to follow the changes in AM and its mRNA levels, respectively; ELISA and reverse transcription-polymerase chain reaction were used to follow the changes in cytokines and their mRNA levels, respectively. 3. In the kidney, the preproAM mRNA levels were increased 1 and 3 h after LPS treatment, whereas AM levels were decreased at 3 h. Interleukin (IL)-6 and IL-1β levels were increased at 3 and 6 h, respectively. 4. The preproAM mRNA levels were elevated in the liver 3 h after LPS injection. Concentrations of tumour necrosis factor (TNF)-α and IL-1β were increased at l and 6 h, respectively. 5. There were no changes in the levels of either preproAM mRNA or AM in the adrenal gland and the spleen. In the spleen, TNF-α levels were elevated at 1 and 3 h after LPS injection and IL-1β was elevated at 1 and 6 h after LPS injection, whereas in the adrenal gland IL-1β was elevated at 6 h after injection. 6. The mRNA levels of the three cytokines were elevated at all three time intervals examined in the kidney, liver, adrenal gland and spleen, with the exception that TNF-α mRNA was not elevated in the adrenal gland at 6 h after LPS injection and IL-1β mRNA was not elevated in the spleen at 3 and 6 h. 7. The plasma concentrations of TNF-α were increased at 1 and 3 h after LPS injection, whereas plasma concentration of IL-1β and IL-6 were elevated at 3 and 6 h for both. 8. The present results suggest that the biosynthesis and secretion of AM may be differentially regulated in various tissues of rats injected with LPS and that AM may interact with cytokines during inflammation. © 2005 Blackwell Publishing Asia Pty Ltd.link_to_subscribed_fulltex

VIP and PACAP in the CNS: regulators of glial energy metabolism and modulators of glutamatergic signaling.

VIP neurons are a homogeneous population of intracortical bipolar cells. They receive excitatory synapses from afferent circuits to the cortex and exert effects on neurons, astrocytes, and capillaries. Effects on the two latter cell types imply that VIP neurons can translate incoming neuronal signals into local metabolic actions. Indeed, VIP tightly regulates glycogen metabolism in astrocytes. In this cell type VIP regulates the expression of a number of genes related to energy metabolism, such as glycogen synthase. These effects of VIP involve the transcription factor family C/EBP and result in the induction of at least seven new proteins by astrocytes. The actions of VIP on neurons appear to be of a modulatory nature: thus VIP enhances glutamate-mediated neurotransmission by potentiating the effects of glutamate on arachidonic acid formation and on the induction of c-fos and on BDNF expression. These effects indicate that VIP can actually increase the strength of glutamate-mediated neurotransmission