Withaferin A Inhibits Helicobacter pylori-induced Production of IL-1β in Dendritic Cells by Regulating NF-κB and NLRP3 Inflammasome Activation

Jae-Eun Kim; Jun-Young Lee; Min-Jung Kang; Yu-Jin Jeong; Jin-A Choi; Sang-Muk Oh; Kyung-Bok Lee; Jong-Hwan Park

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자료유형: 학술저널

저자정보: Jae-Eun Kim (Konyang University) Jun-Young Lee (Chonnam National University) Min-Jung Kang (Chonnam National University) Yu-Jin Jeong (Konyang University) Jin-A Choi (Konyang University) Sang-Muk Oh (Konyang University) Kyung-Bok Lee (Konyang University) Jong-Hwan Park (Chonnam National University)

저널정보: 대한면역학회 Immune Network Immune Network Vol.15 No.6

발행연도: 2015.12

수록면: 269 - 277 (9page)

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Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. There is evidence that IL-1β is associated with the development of gastric cancer. Therefore, downregulation of H. pylori-mediated IL-1β production may be a way to prevent gastric cancer. Withaferin A (WA), a withanolide purified from Withania somnifera, is known to exert anti-inflammatory and anti-tumor effects. In the present study, we explored the inhibitory activity of WA on H. pylori-induced production of IL-1β in murine bone marrow-derived dendritic cells (BMDCs) and the underlying cellular mechanism. Cotreatment with WA decreased IL-1β production by H. pylori in BMDCs in a dose-dependent manner. H. pylori-induced gene expression of IL-1β and NLRP3 (NOD-like receptor family, pyrin domain containing 3) were also suppressed by WA treatment. Moreover, IκB-α phosphorylation by H. pylori infection was suppressed by WA in BMDCs. Western blot analysis revealed that H. pylori induced cleavage of caspase-1 and IL-1β, as well as increased procaspase-1 and pro IL-1β protein levels, and that both were suppressed by co-treatment with WA. Finally, we determined whether WA can directly inhibit activation of the NLRP3 inflammasome. NLRP3 activators induced IL-1β secretion in LPS-primed macrophages, which was inhibited by WA in a dose-dependent manner, whereas IL-6 production was not affected by WA. Moreover, cleavage of IL-1β and caspase-1 by NLRP3 activators was also dose-dependently inhibited by WA. These findings suggest that WA can inhibit IL-1β production by H. pylori in dendritic cells and can be used as a new preventive and therapeutic agent for gastric cancer.

#Dendritic cells #Helicobacter pylori #Interleukin 1β #NLRP3 inflammasome #Withaferin A

참고문헌 (66)

참고문헌 신청

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이 논문의 저자 정보

Jae-Eun Kim

소속기관 Konyang University

주요연구분야 의약학 > 기초의학 > 면역학

논문수 1 이용수 13

Jun-Young Lee

소속기관 Chonnam National University