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- W2019966807 endingPage "138" @default.
- W2019966807 startingPage "125" @default.
- W2019966807 abstract "Mediators such as prostaglandin E2 (PGE2) and norepinephrine (NE) regulate macrophage (Mφ) responsiveness. Activation of α2-adrenergic receptors on Mφ potentiates lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNFα) production. PGE2 inhibits LPS-stimulated TNFα production and gene expression, a response that can be desensitized by pretreatment of Mφ with PGE2. We have determined that concomitant pretreatment of Mφ with PGE2 and the α2-adrenergic agonist UK-14304 (UK) can prevent the PGE2-induced desensitization. PGE2 concentration–effect curves have been determined for the inhibition of LPS-stimulated TNFα production by murine peritoneal Mφ. The addition of 10 nM UK to Mφ in culture significantly shifts the PGE2 concentration–effect curve to the right; pretreatment of Mφ with UK significantly shifts the PGE2 concentration–effect curve to the left; and pretreatment with the cyclooxygenase inhibitor, indomethacin, increases the maximum response of PGE2. Preincubation of Mφ with PGE2 (0.5 h) followed by washing significantly shifts the subsequent PGE2 concentration–effect curve to the right. Concomitant preincubation of Mφ with PGE2 and UK prevents this rightward shift, an effect that is blocked by the α2-adrenergic receptor antagonist yohimbine. Northern blot analysis demonstrates that UK increases LPS-induced TNFα mRNA accumulation, and this is blocked by yohimbine, while PGE2 decreases TNFα mRNA accumulation. Preincubation of Mφ with PGE2 prevents PGE2 regulation of TNFα mRNA, and concomitant preincubation of Mφ with PGE2 and UK reverses this effect. These investigations support the role of NE as a regulator of Mφ TNFα production, a response that has functional interactions with Mφ sensitivity to PGE2." @default.
- W2019966807 created "2016-06-24" @default.
- W2019966807 creator A5002068485 @default.
- W2019966807 creator A5075492017 @default.
- W2019966807 date "1992-01-01" @default.
- W2019966807 modified "2023-10-16" @default.
- W2019966807 title "Tumour necrosis factor α (TNF) in neuroimmunology" @default.
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