The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock

Biochem Biophys Res Commun. 2006 Mar 24;341(4):1149-54. doi: 10.1016/j.bbrc.2006.01.075. Epub 2006 Jan 26.

Abstract

Neuromedin U (NMU) is a neuropeptide involved in appetite, circadian rhythm, and pronociception. However, the NMU receptor NMU-R1 has been shown to be expressed in immune cells and NMU promotes mast cell-dependent inflammation. In this study, we demonstrated that NMU plays an important role in IL-6 production in macrophages. NMU-deficient mice were resistant against cecal ligation puncture- as well as LPS-induced septic shock. IL-6 but not TNF-alpha levels were markedly reduced in LPS-treated NMU-deficient mice compared with wild type mice. Both NMU and NMU-R1 were expressed in wild type peritoneal macrophages, and treatment with LPS resulted in up-regulation of NMU but down-regulation of NMU-R1 expression, however, no down-regulation of NMU-R1 was observed in NMU-deficient macrophages where LPS-induced IL-6 production was severely reduced. These data suggest that LPS-induced IL-6 expression is partly dependent on autocrine/paracrine activation of the NMU-NMU-R1 signals in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cecum / surgery
  • Interleukin-6 / biosynthesis*
  • Ligation
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / physiology*
  • Mice
  • Mice, Knockout
  • Neuropeptides / deficiency
  • Neuropeptides / physiology*
  • Punctures
  • Shock, Septic / chemically induced
  • Shock, Septic / prevention & control*

Substances

  • Interleukin-6
  • Lipopolysaccharides
  • Neuropeptides
  • neuromedin U