論文 - 詳細
| RRC ID | 18671 |
|---|---|
| 著者 | Shikama Y, Kuroishi T, Nagai Y, Iwakura Y, Shimauchi H, Takada H, Sugawara S, Endo Y. |
| タイトル | 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). |
| ジャーナル | Innate Immun |
| 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)-γ. 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). |
| 巻・号 | 17(1) |
| ページ | 3-15 |
| 公開日 | 2011-2-1 |
| DOI | 10.1177/1753425909347508 |
| PII | 1753425909347508 |
| PMID | 19897531 |
| MeSH | Acetylmuramyl-Alanyl-Isoglutamine / administration & dosage Acetylmuramyl-Alanyl-Isoglutamine / pharmacology* Animal Structures / drug effects Animal Structures / metabolism Animals Body Temperature / drug effects Caspase 1 / metabolism Cell Line, Tumor Clodronic Acid / pharmacology Down-Regulation / drug effects* Down-Regulation / physiology Drug Synergism Gene Expression / drug effects Gene Expression / genetics Interferon-gamma / blood Interleukin-12 Subunit p40 / blood Interleukin-12 Subunit p40 / metabolism Interleukin-1alpha / genetics Interleukin-1beta / blood Interleukin-1beta / genetics Interleukin-1beta / metabolism* Lipopolysaccharides / administration & dosage Lipopolysaccharides / pharmacology* Macrophages / drug effects Macrophages / metabolism* Male Mice Mice, Inbred BALB C Mice, Knockout Protein Precursors / genetics Protein Precursors / metabolism* Shock, Septic / chemically induced Shock, Septic / physiopathology Spleen / drug effects Spleen / metabolism Spleen / pathology Suppressor of Cytokine Signaling 1 Protein Suppressor of Cytokine Signaling Proteins / genetics Suppressor of Cytokine Signaling Proteins / metabolism* Tumor Necrosis Factor-alpha / blood Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism |
| IF | 2.298 |
| 引用数 | 17 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL MICROBIOLOGY IMMUNOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |