The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock.
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.
Moriyama
Maiko
M
Department of Molecular Genetics, Institute of Life Sciences, Kurume University, 1-1 Hyakunen-kohen, Kurume, Fukuoka, Japan. moriyama@lsi.kurume-u.ac.jp
Matsukawa
Akihiro
A
Kudoh
Shinji
S
Takahashi
Tomoko
T
Sato
Takahiro
T
Kano
Tatsuhiko
T
Yoshimura
Akihiko
A
Kojima
Masayasu
M
D000818:Animals; D002432:Cecum / Q000601:surgery; D015850:Interleukin-6 / Q000096:biosynthesis*; D008026:Ligation; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000172:deficiency / Q000502:physiology*; D011677:Punctures; D012772:Shock, Septic / Q000139:chemically induced / Q000517:prevention & control*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D009479:Neuropeptides; C056900:neuromedin U