Diacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes protein kinase C phosphorylation and histamine-mediated signaling in the mammalian intestinal epithelium.
Diacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes protein kinase C phosphorylation and histamine-mediated signaling in the mammalian intestinal epithelium.
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由共生乳杆菌REUTERI合成的二酰基甘油激酶减少了哺乳动物肠道上皮的蛋白激酶C磷酸化和组胺介导的信号传导。
DOI：
10.1038/mi.2017.58
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发表时间：
2018-03
影响因子：
8
通讯作者：
Versalovic J
中科院分区：
文献类型：
--
作者：
Ganesh BP;Hall A;Ayyaswamy S;Nelson JW;Fultz R;Major A;Haag A;Esparza M;Lugo M;Venable S;Whary M;Fox JG;Versalovic J
人类微生物组的罗伊氏乳杆菌6475（Lr）合成组胺，并且可以通过哺乳动物肠道中的2型组胺受体（H2 R）活化来抑制炎症。肠道微生物如Lr促进H2 R信号传导，并可能通过未知机制平行抑制H1 R促炎信号传导途径。在这项研究中，我们确定了一种可溶性细菌酶，称为二酰基甘油激酶（DGK）从Lr分泌到细胞外环境，并推测到肠腔。DgK通过促进其代谢转化并导致哺乳动物细胞中PKC磷酸化（pPKC）减少而减少哺乳动物细胞中的二酰基甘油（DAG）量，作为哺乳动物细胞中的净效应。我们证明了肠道微生物（Lr）合成的组胺激活哺乳动物H1 R和H2 R，但Lr衍生的Dgk抑制H1 R信号通路。WT Lr处理的小鼠和人肠上皮内磷酸化PKC和IκBα减少，但ΔdgkA Lr处理的pPKC和IκBα未减少。在WT Lr中，粘液IL-6和全身IL-1α、嗜酸性粒细胞趋化因子和G-CSF受到抑制，但在ΔdgkA Lr定殖小鼠中没有。总的来说，肠道微生物Lr可以通过减少pPKC介导的哺乳动物细胞信号传导抑制肠道H1 R介导的促炎反应来充当“微生物抗组胺剂”。
Lactobacillus reuteri 6475 (Lr) of the human microbiome synthesizes histamine and can suppress inflammation via type 2 histamine receptor (H2R) activation in the mammalian intestine. Gut microbes such as Lr promote H2R signaling and may suppress H1R pro-inflammatory signaling pathways in parallel by unknown mechanisms. In this study, we identified a soluble bacterial enzyme known as diacylglycerol kinase (Dgk) from Lr that is secreted into the extracellular milieu and presumably into the intestinal lumen. DgK diminishes diacylglycerol (DAG) quantities in mammalian cells by promoting its metabolic conversion and causing reduced PKC phosphorylation (pPKC) as a net effect in mammalian cells. We demonstrated that histamine synthesized by gut microbes (Lr) activates both mammalian H1R and H2R, but Lr-derived Dgk suppresses the H1R signaling pathway. Phospho-PKC and IκBα were diminished within the intestinal epithelium of mice and humans treated by WT Lr, but pPKC and IκBα were not decreased in treatment with ΔdgkA Lr. Mucosal IL-6 and systemic IL-1α, eotaxin and G-CSF were suppressed in WT Lr, but not in ΔdgkA Lr colonized mice. Collectively, the commensal microbe Lr may act as a “microbial antihistamine” by suppressing intestinal H1R mediated pro-inflammatory responses via diminished pPKC-mediated mammalian cell signaling.
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影响因子：
8
作者：
Guillet, R;Stoll, BJ;Phelps, DL
通讯作者：
Phelps, DL
影响因子：
3.1
作者：
Ferstl, Ruth;Akdis, Cezmi A.;O'Mahony, Liam
通讯作者：
O'Mahony, Liam
DOI：
10.1038/jid.2011.406
发表时间：
2012-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Mascia F;Denning M;Kopan R;Yuspa SH
通讯作者：
Yuspa SH
DOI：
10.1073/pnas.1604841113
发表时间：
2016-05-10
影响因子：
11.1
作者：
Fabbri, Roberta;Furini, Cristiane Regina Guerino;Blandina, Patrizio
通讯作者：
Blandina, Patrizio
影响因子：
13.8
作者：
ASAOKA, Y;NAKAMURA, S;NISHIZUKA, Y
通讯作者：
NISHIZUKA, Y