Muramyldipeptide augments the actions of lipopolysaccharide in mice by stimulating macrophages to produce pro-IL-1β and by down-regulation of the suppressor of cytokine signaling 1 (SOCS1)

Yosuke Shikama, Toshinobu Kuroishi, Yasuhiro Nagai, Yoichiro Iwakura, Hidetoshi Shimauchi, Haruhiko Takada, Shunji Sugawara, Yasuo Endo

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Muramyldipeptide (MDP), the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2). Muramyldipeptide enhances the activities of lipopolysaccharide (LPS), but the mechanism underlying this effect is unclear. Here, we obtained evidence that intravenously injected MDP augments LPS-induced hypothermia in wild-type mice, but not in mice deficient in interleukin (IL)-1α/β and/or tumor-necrosis factor (TNF)-α. Muramyldipeptide also: (i) increased pro-IL-1β in tissues, but did not increase IL-1β in serum (since caspase-1 was not activated by MDP); (ii) downregulated the expression of suppressor of cytokine signaling 1 (SOCS1; a negative-feedback regulator of LPS-induced signaling); and (iii) augmented the LPS-induced production of TNF-α, IL-12 p40, and interferon (IFN)-?. Moreover, by performing in vivo and in vitro experiments, we obtained evidence that macrophages were involved in these effects of MDP. These results suggest that two different mechanisms may underlie the augmenting effect of MDP: namely, stimulation of pro-IL-1β production by, and down-regulation of SOCS1 in, macrophages. We consider that this work may help to elucidate the pathogenesis of mixed bacterial infections, including septic shock and multiple organ dysfunction syndrome (MODS).

Original languageEnglish
Pages (from-to)3-15
Number of pages13
JournalInnate Immunity
Volume17
Issue number1
DOIs
Publication statusPublished - 2010 Feb

Keywords

  • LPS
  • MDP
  • SOCS1
  • inflammatory cytokines
  • macrophage

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Muramyldipeptide augments the actions of lipopolysaccharide in mice by stimulating macrophages to produce pro-IL-1β and by down-regulation of the suppressor of cytokine signaling 1 (SOCS1)'. Together they form a unique fingerprint.

  • Cite this