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


ABSTRACT: 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.

SUBMITTER: Murakami K 

PROVIDER: S-EPMC8185171 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Murakami Kaoru K   Kamimura Daisuke D   Hasebe Rie R   Uchida Mona M   Abe Nobuya N   Yamamoto Reiji R   Jiang Jing-Jing JJ   Hidaka Yasuhiro Y   Nakanishi Yuko Y   Fujita Shuzo S   Toda Yuki Y   Toda Nobuhiro N   Tanaka Hiroki H   Akira Shizuo S   Tanaka Yuki Y   Murakami Masaaki M  

Frontiers in immunology 20210525


The lipopolysaccharides (LPSs) of <i>Rhodobacter</i> are reported to be TLR4 antagonists. Accordingly, the extract of <i>Rhodobacter azotoformans</i> (RAP99) is used as a health supplement for humans and animals in Japan to regulate immune responses <i>in vivo</i>. We previously analyzed the LPS structure of RAP99 (RAP99-LPS) and found it is different from that of <i>E. coli</i>-LPS but similar to lipid A from <i>Rhodobacter sphaeroides</i> (RSLA), a known antagonist of TLR4, with both having th  ...[more]

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