Cucurbitacin D is a new inflammasome activator in macrophages
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- 作者：Yuan Song ; Ning Ding ; Tamotsu Kanazawa ; Uki Yamashita ; Yasuhiro Yoshida
- 关键词：THMs ; traditional medicinal herbs ; PECs ; peritoneal exudate cells ; BMDMs ; bone marrow derived macrophages ; MAPKs ; mitogen-activated protein kinases ; NALP3 ; NOD-like receptor family ; pyrin domain containing 3 ; ASC ; apoptosis-associated speck-like protein containing a caspase-activating and recruitment domain ; TLR ; Toll-like receptor ; LDH ; lactate dehydrogenase
- 刊名：International Immunopharmacology
- 出版年：December, 2013
- 年：2013
- 卷：17
- 期：4
- 页码：1044-1050
- 全文大小：795 K
文摘
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)-1尾 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-1尾 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.