Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling.
Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling.
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源自益生菌乳酸杆菌的组胺通过调节PKA和ERK信号传导抑制TNF。
DOI：
10.1371/journal.pone.0031951
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Versalovic J
中科院分区：
文献类型：
--
作者：
Thomas CM;Hong T;van Pijkeren JP;Hemarajata P;Trinh DV;Hu W;Britton RA;Kalkum M;Versalovic J
有益微生物和益生菌物种，如罗伊氏乳杆菌，产生生物活性化合物，可以调节宿主粘膜免疫。以前，罗伊氏乳杆菌ATCC PTA 6475分泌的免疫调节因子是未知的。利用代谢组学和细菌遗传学相结合的策略来鉴定罗伊氏乳杆菌产生的抑制tnf的小化合物。亲水相互作用液相色谱-高效液相色谱（HILIC-HPLC）分离分离tnf -抑制化合物，并通过NMR和质谱分析确定HILIC-HPLC组分的组成。组胺在抑制tnf的HILIC-HPLC中进行鉴定和定量。组胺是由l -组氨酸通过组氨酸脱羧酶产生的，一些发酵细菌包括乳酸菌。对罗伊氏乳杆菌6475组氨酸脱羧酶基因簇中存在的每个基因进行靶向诱变，表明组氨酸脱羧酶丙酮酰A型（hdcA）、组氨酸/组胺反转运蛋白（hdcP）和hdcB参与了tnf抑制因子的产生。利用toll样受体2 （TLR2）激活的人单核细胞，研究罗伊氏乳杆菌源组胺抑制TNF的机制。细菌组胺通过激活H2受体抑制TNF的产生。来自罗伊氏乳杆菌6475的组胺刺激cAMP水平升高，从而通过蛋白激酶A （PKA）抑制下游MEK/ERK MAPK信号传导，并通过转录调控抑制TNF的产生。总之，肠道微生物组的一种成分罗伊氏乳杆菌能够将膳食成分l -组氨酸转化为免疫调节信号组胺，从而抑制促炎TNF的产生。细菌生物活性代谢物的鉴定及其在免疫调节方面的相应作用机制可能导致改善慢性免疫介导疾病的抗炎策略。
Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.
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影响因子：
2.8
作者：
Hungerford, James M.
通讯作者：
Hungerford, James M.
影响因子：
4.4
作者：
Christensen, HR;Frokiær, H;Pestka, JJ
通讯作者：
Pestka, JJ
影响因子：
8
作者：
Guillet, R;Stoll, BJ;Phelps, DL
通讯作者：
Phelps, DL
影响因子：
3.9
作者：
Gionchetti, Paolo;Rizzello, Fernando;Campieri, Massimo
通讯作者：
Campieri, Massimo
DOI：
10.1152/ajpgi.00572.2004
发表时间：
2005-06-01
影响因子：
4.5
作者：
Clarke, MB;Sperandio, V
通讯作者：
Sperandio, V