PMID- 25499802
OWN - NLM
STAT- MEDLINE
DCOM- 20150304
LR  - 20150102
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 64
IP  - 1
DP  - 2015 Mar
TI  - Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, promotes TNF-alpha 
      production via nucleotide-binding oligomerization domain containing 2 
      (Nod2)-dependent NF-kappaB activation in RAW264.7 cells.
PG  - 218-27
LID - S0161-5890(14)00329-0 [pii]
LID - 10.1016/j.molimm.2014.11.017 [doi]
AB  - Macrophages are a major component of the innate immune system, and the cytokines 
      they secrete are involved in antitumor responses. Z-100 is obtained from 
      hot-water extract of human-type Mycobacterium tuberculosis strain Aoyama B and 
      activates the innate immune response. However, while Z-100 is known to modulate 
      macrophage activity, the mechanism behind this modulation is not fully 
      understood. We evaluated the effects of Z-100 on the murine macrophage cell line 
      RAW264.7. Tumor necrosis factor-alpha (TNF-alpha) production from RAW264.7 cells was 
      strongly induced by Z-100 and interferon-gamma (IFN-gamma) stimulation but only 
      weakly induced by Z-100 alone. Quantitative gene expression analysis showed that 
      nucleotide-binding oligomerization domain containing 2 (Nod2) expression was 
      up-regulated by IFN-gamma treatment in RAW264.7 cells while Z-100-induced TNF-alpha 
      production was attenuated by Nod2 gene silencing. Further, componential analysis 
      demonstrated that muramic acid and amino acids distinctive of muramyl dipeptide 
      (MDP) were contained within Z-100 and Z-100Fr I, the low-molecular-weight 
      fraction containing components <3 kDa in size. In addition, Z-100Fr I enhanced 
      TNF-alpha production in RAW264.7 cells and promoted NOD2-dependent nuclear 
      factor-kappa B (NF-kappaB) activation in murine NOD2-expressing SEAP reporter HEK293 
      (HEK-Blue-mNOD2) cells. Taken together, these results suggest that Z-100 contains 
      MDP-like molecules and augments NF-kappaB signaling via the direct activation of Nod2 
      in macrophages, which might be one mechanism driving the innate immune responses 
      induced by Z-100 in cancer immunotherapy.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Katsunuma, Kokichi
AU  - Katsunuma K
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan. Electronic address: 
      koukichi-katsunuma@zeria.co.jp.
FAU - Yoshinaga, Koji
AU  - Yoshinaga K
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan.
FAU - Ohira, Yuta
AU  - Ohira Y
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan.
FAU - Eta, Runa
AU  - Eta R
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan.
FAU - Sato, Takanori
AU  - Sato T
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan.
FAU - Horii, Takayuki
AU  - Horii T
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan.
FAU - Tanaka, Takao
AU  - Tanaka T
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan.
FAU - Takei, Mineo
AU  - Takei M
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan.
FAU - Seto, Koichi
AU  - Seto K
AD  - Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, 
      Oshikiri, Kumagaya City 360-0111, Saitama, Japan.
LA  - eng
PT  - Journal Article
DEP - 20141208
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Lipids)
RN  - 0 (Mannans)
RN  - 0 (NF-kappa B)
RN  - 0 (Nod2 Signaling Adaptor Protein)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (specific substance maruyama)
RN  - 53678-77-6 (Acetylmuramyl-Alanyl-Isoglutamine)
SB  - IM
MH  - Acetylmuramyl-Alanyl-Isoglutamine/pharmacology
MH  - Animals
MH  - Cell Line
MH  - Lipids/chemistry/*isolation & purification/*pharmacology
MH  - Macrophages/drug effects/*metabolism
MH  - Mannans/chemistry/*isolation & purification/*pharmacology
MH  - Mice
MH  - Molecular Weight
MH  - Mycobacterium tuberculosis/*chemistry
MH  - NF-kappa B/*metabolism
MH  - Nod2 Signaling Adaptor Protein/*metabolism
MH  - Protein Transport/drug effects
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
OTO - NOTNLM
OT  - Macrophages
OT  - NF-kappaB
OT  - Nod2
OT  - Z-100
EDAT- 2014/12/17 06:00
MHDA- 2015/03/05 06:00
CRDT- 2014/12/16 06:00
PHST- 2014/07/24 00:00 [received]
PHST- 2014/11/20 00:00 [revised]
PHST- 2014/11/25 00:00 [accepted]
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/03/05 06:00 [medline]
AID - S0161-5890(14)00329-0 [pii]
AID - 10.1016/j.molimm.2014.11.017 [doi]
PST - ppublish
SO  - Mol Immunol. 2015 Mar;64(1):218-27. doi: 10.1016/j.molimm.2014.11.017. Epub 2014 
      Dec 8.