| Title: | Rhodobacter azotoformans LPS (RAP99-LPS) Is a TLR4 Agonist That Inhibits Lung Metastasis and Enhances TLR3-Mediated Chemokine Expression |
| Authors: | Murakami, Kaoru Browse this author |
| Kamimura, Daisuke Browse this author |
| Hasebe, Rie Browse this author |
| Uchida, Mona Browse this author |
| Abe, Nobuya Browse this author |
| Yamamoto, Reiji Browse this author |
| Jiang, Jing-Jing Browse this author |
| Hidaka, Yasuhiro Browse this author |
| Nakanishi, Yuko Browse this author |
| Fujita, Shuzo Browse this author |
| Toda, Yuki Browse this author |
| Toda, Nobuhiro Browse this author |
| Tanaka, Hiroki Browse this author |
| Akira, Shizuo Browse this author |
| Tanaka, Yuki Browse this author |
| Murakami, Masaaki Browse this author →KAKEN DB |
| Keywords: | RAP99-LPS |
| TLR4 |
| agonist |
| NF-kB |
| STAT3 |
| Issue Date: | 25-May-2021 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in immunology |
| Volume: | 12 |
| Start Page: | 675909 |
| Publisher DOI: | 10.3389/fimmu.2021.675909 |
| 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82229 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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