Rhodobacter azotoformans LPS (RAP99-LPS) Is a TLR4 Agonist That Inhibits Lung Metastasis and Enhances TLR3-Mediated Chemokine Expression
| Autor: | Hiroki Tanaka, Mona Uchida, Yuki Tanaka, Nobuya Abe, Reiji Yamamoto, Kaoru Murakami, Nobuhiro Toda, Shuzo Fujita, Yasuhiro Hidaka, Jing-Jing Jiang, Masaaki Murakami, Yuko Nakanishi, Shizuo Akira, Rie Hasebe, Yuki Toda, Daisuke Kamimura |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Agonist
Chemokine RAP99-LPS medicine.drug_class Immunology Lipid A STAT3 Rhodobacter sphaeroides Immune system medicine Immunology and Allergy TLR4 NF-kB agonist Original Research Rhodobacter biology Chemistry RC581-607 biology.organism_classification Molecular biology TLR3 biology.protein lipids (amino acids peptides and proteins) Immunologic diseases. Allergy |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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