PMID- 24140411
OWN - NLM
STAT- MEDLINE
DCOM- 20140902
LR  - 20161128
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 17
IP  - 4
DP  - 2013 Dec
TI  - Cucurbitacin D is a new inflammasome activator in macrophages.
PG  - 1044-50
LID - S1567-5769(13)00371-8 [pii]
LID - 10.1016/j.intimp.2013.10.003 [doi]
AB  - We previously reported that cucurbitacin D isolated from Trichosanthes kirilowii 
      has anti-tumor roles to leukemia cells. However, the effect of cucurbitacin D on 
      immune cells is not fully understood although there is no toxic activity to 
      normal cells. In this study, immunomodulating activities of cucurbitacin D were 
      investigated in macrophages. Cucurbitacin D could increase LPS-induced 
      interleukin (IL)-1beta production in culture supernatant of THP-1 cells, peritoneal 
      exudate cells (PECs), bone marrow derived macrophages (BMDMs), and RAW264 cells. 
      At the transcriptional level, cucurbitacin D enhanced LPS-induced IL-1beta mRNA 
      expression through activation of ERK1/2 mitogen-activated protein kinases 
      (MAPKs). At the posttranscriptional level, the activation of caspase-1 induced by 
      cucurbitacin D has also been demonstrated following treatment with a caspase-1 
      inhibitor and siRNA. Importantly, cucurbitacin D has further been shown to induce 
      inflammasome activation independent of ERK1/2 activation. Western blotting showed 
      interaction of NOD-like receptor family, pyrin domain containing 3 (NALP3) and 
      apoptosis-associated speck-like protein containing a caspase-activating and 
      recruitment domain (ASC), suggesting activation of the inflammasome and a 
      possible reason for activation of caspase-1. Taken together, these results 
      suggest that cucurbitacin D could initiate immunomodulating activity in 
      macrophages to lead to inflammasome activation as well as enhancement of LPS 
      signaling.
CI  - (c) 2013.
FAU - Song, Yuan
AU  - Song Y
AD  - Department of Immunology and Parasitology, School of Medicine, University of 
      Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, 
      Kitakyushu 807-8555, Japan.
FAU - Ding, Ning
AU  - Ding N
FAU - Kanazawa, Tamotsu
AU  - Kanazawa T
FAU - Yamashita, Uki
AU  - Yamashita U
FAU - Yoshida, Yasuhiro
AU  - Yoshida Y
LA  - eng
PT  - Journal Article
DEP - 20131016
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Immunologic Factors)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Triterpenes)
RN  - 5I62H4ORC7 (cucurbitacin D)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Immunologic Factors/*pharmacology
MH  - Inflammasomes/drug effects/immunology
MH  - Interleukin-1beta/genetics/*immunology
MH  - Lipopolysaccharides
MH  - Macrophages/*drug effects/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mitogen-Activated Protein Kinase 1/immunology
MH  - Mitogen-Activated Protein Kinase 3/immunology
MH  - Triterpenes/*pharmacology
OTO - NOTNLM
OT  - ASC
OT  - BMDMs
OT  - Cucurbitacin D
OT  - ERK1/2
OT  - IL-1beta
OT  - Inflammasome
OT  - LDH
OT  - MAPKs
OT  - Macrophages
OT  - NALP3
OT  - NOD-like receptor family, pyrin domain containing 3
OT  - PECs
OT  - THMs
OT  - TLR
OT  - Toll-like receptor
OT  - apoptosis-associated speck-like protein containing a caspase-activating and 
      recruitment domain
OT  - bone marrow derived macrophages
OT  - lactate dehydrogenase
OT  - mitogen-activated protein kinases
OT  - peritoneal exudate cells
OT  - traditional medicinal herbs
EDAT- 2013/10/22 06:00
MHDA- 2014/09/03 06:00
CRDT- 2013/10/22 06:00
PHST- 2013/08/21 00:00 [received]
PHST- 2013/09/30 00:00 [revised]
PHST- 2013/10/03 00:00 [accepted]
PHST- 2013/10/22 06:00 [entrez]
PHST- 2013/10/22 06:00 [pubmed]
PHST- 2014/09/03 06:00 [medline]
AID - S1567-5769(13)00371-8 [pii]
AID - 10.1016/j.intimp.2013.10.003 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2013 Dec;17(4):1044-50. doi: 10.1016/j.intimp.2013.10.003. 
      Epub 2013 Oct 16.