Rhodobacter azotoformans LPS (RAP99-LPS) Is a TLR4 Agonist That Inhibits Lung Metastasis and Enhances TLR3-Mediated Chemokine Expression.

Rhodobacter azotoformans LPS (RAP99-LPS) Is a TLR4 Agonist That Inhibits Lung Metastasis and Enhances TLR3-Mediated Chemokine Expression.
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DOI:
10.3389/fimmu.2021.675909
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发表时间:
2021
影响因子:
7.3
通讯作者:
Murakami M
Murakami M
中科院分区:
医学2区
文献类型:
--
作者:
Murakami K;Kamimura D;Hasebe R;Uchida M;Abe N;Yamamoto R;Jiang JJ;Hidaka Y;Nakanishi Y;Fujita S;Toda Y;Toda N;Tanaka H;Akira S;Tanaka Y;Murakami M

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据报道,红细菌属的脂多糖(LPS)是TLR 4拮抗剂。因此,在日本,固氮红杆菌(Rhodobacter azotoformans)的提取物(RAP 99)被用作人和动物的健康补充剂,以调节体内免疫应答。我们对RAP 99(RAP 99-LPS)的LPS结构进行了分析,发现其与大肠杆菌的LPS结构不同。coli-LPS,但类似于来自类球红杆菌(Rhodobacter sphaeroides,RSLA)的脂质A,其是一种已知的TLR 4拮抗剂,两者都具有三个C14脂肪酰基、两个C10脂肪酰基和两个磷酸。在这里,我们表明,RAP 99-LPS具有免疫刺激活性,并作为TLR 4激动剂。RAP 99-LPS预处理抑制E. coli-LPS介导的体重减轻作用,提示它是一种抗大肠杆菌的拮抗剂。coli-LPS类似于从红细菌属分离的其他LPS。然而,注射RAP 99-LPS在C57 BL/6小鼠中引起脾肿大和免疫细胞数量增加,但在C3 H/HeJ小鼠中不引起,表明RAP 99-LPS通过TLR 4刺激免疫细胞。结论:RAP 99-LPS可抑制B16 F1肿瘤细胞的肺转移,并增强TLR 3介导的趋化因子的表达。这些结果表明,RAP 99-LPS是一种TLR 4激动剂,其增强免疫系统的活化状态以促进体内抗病毒和抗肿瘤活性。
The lipopolysaccharides (LPSs) of Rhodobacter are reported to be TLR4 antagonists. Accordingly, the extract of Rhodobacter azotoformans (RAP99) is used as a health supplement for humans and animals in Japan to regulate immune responses in vivo. We previously analyzed the LPS structure of RAP99 (RAP99-LPS) and found it is different from that of E. coli-LPS but similar to lipid A from Rhodobacter sphaeroides (RSLA), a known antagonist of TLR4, with both having three C14 fatty acyl groups, two C10 fatty acyl groups, and two phosphates. Here we show that RAP99-LPS has an immune stimulatory activity and acts as a TLR4 agonist. Pretreatment of RAP99-LPS suppressed E. coli-LPS-mediated weight loss, suggesting it is an antagonist against E. coli-LPS like other LPS isolated from Rhodobacter. However, injections of RAP99-LPS caused splenomegaly and increased immune cell numbers in C57BL/6 mice but not in C3H/HeJ mice, suggesting that RAP99-LPS stimulates immune cells via TLR4. Consistently, RAP99-LPS suppressed the lung metastasis of B16F1 tumor cells and enhanced the expression of TLR3-mediated chemokines. These results suggest that RAP99-LPS is a TLR4 agonist that enhances the activation status of the immune system to promote anti-viral and anti-tumor activity in vivo.
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