Chemical Synthesis of helicobacter pylori lipopolysaccharide partial structures and their selective proinflammatory responses

Atsushi Shimoyama, Akinori Saeki, Natsuko Tanimura, Hiroko Tsutsui, Kensuke Miyake, Yasuo Suda, Yukari Fujimoto, Koichi Fukase

研究成果: Article

34 引用 (Scopus)

抄録

Helicobacter pylori is a common cause of gastroduodenal inflammatory diseases such as chronic gastritis and peptic ulcers and also an important factor in gastric carcinogenesis. Recent reports have demonstrated that bacterial inflammatory processes, such as stimulation with H. pylori lipopolysaccharide (LPS), initiate atherosclerosis. To establish the structures responsible for the inflammatory response of H. pylori LPS, we synthesized various kinds of lipid A structures (i.e., triacylated lipid A and Kdo-lipid A compounds), with or without the ethanolamine group at the 1-phosphate moiety, by a new divergent synthetic route. Stereoselective α-glycosylation of Kdo N-phenyltrifluoroacetimidate was achieved by use of microfluidic methods. None of the lipid A and Kdo-lipid A compounds were a strong inducer of IL-1β, IL-6, or IL-8, suggesting that H. pylori LPS is unable to induce acute inflammation. In fact, the lipid A and Kdo-lipid A compounds showed antagonistic activity against cytokine induction by E. coli LPS, except for the lipid A compound with the ethanolamine group, which showed very weak agonistic activity. On the other hand, these H. pylori LPS partial structures showed potent IL-18- and IL-12-inducing activities. IL-18 has been shown to correlate with chronic inflammation, so H. pylori LPS might be implicated in the chronic inflammatory responses induced by H. pylori. These results also indicated that H. pylori LPS can modulate the immune response: NF-κB activation through hTLR4/MD-2 was suppressed, whereas production of IL-18 and IL-12 was promoted.

元の言語English
ページ(範囲)14464-14474
ページ数11
ジャーナルChemistry - A European Journal
17
発行部数51
DOI
出版物ステータスPublished - 2011 12 16
外部発表Yes

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Lipid A
Lipids
Lipopolysaccharides
Interleukin-18
Ethanolamines
Ethanolamine
Interleukin-12
Glycosylation
Helicobacter pylori lipopolysaccharide
Interleukin-8
Interleukin-1
Microfluidics
Escherichia coli
Interleukin-6
Phosphates
Chemical activation
Cytokines

ASJC Scopus subject areas

  • Chemistry(all)

これを引用

Chemical Synthesis of helicobacter pylori lipopolysaccharide partial structures and their selective proinflammatory responses. / Shimoyama, Atsushi; Saeki, Akinori; Tanimura, Natsuko; Tsutsui, Hiroko; Miyake, Kensuke; Suda, Yasuo; Fujimoto, Yukari; Fukase, Koichi.

:: Chemistry - A European Journal, 巻 17, 番号 51, 16.12.2011, p. 14464-14474.

研究成果: Article

Shimoyama, Atsushi ; Saeki, Akinori ; Tanimura, Natsuko ; Tsutsui, Hiroko ; Miyake, Kensuke ; Suda, Yasuo ; Fujimoto, Yukari ; Fukase, Koichi. / Chemical Synthesis of helicobacter pylori lipopolysaccharide partial structures and their selective proinflammatory responses. :: Chemistry - A European Journal. 2011 ; 巻 17, 番号 51. pp. 14464-14474.
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AU - Miyake, Kensuke

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AU - Fukase, Koichi

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AB - Helicobacter pylori is a common cause of gastroduodenal inflammatory diseases such as chronic gastritis and peptic ulcers and also an important factor in gastric carcinogenesis. Recent reports have demonstrated that bacterial inflammatory processes, such as stimulation with H. pylori lipopolysaccharide (LPS), initiate atherosclerosis. To establish the structures responsible for the inflammatory response of H. pylori LPS, we synthesized various kinds of lipid A structures (i.e., triacylated lipid A and Kdo-lipid A compounds), with or without the ethanolamine group at the 1-phosphate moiety, by a new divergent synthetic route. Stereoselective α-glycosylation of Kdo N-phenyltrifluoroacetimidate was achieved by use of microfluidic methods. None of the lipid A and Kdo-lipid A compounds were a strong inducer of IL-1β, IL-6, or IL-8, suggesting that H. pylori LPS is unable to induce acute inflammation. In fact, the lipid A and Kdo-lipid A compounds showed antagonistic activity against cytokine induction by E. coli LPS, except for the lipid A compound with the ethanolamine group, which showed very weak agonistic activity. On the other hand, these H. pylori LPS partial structures showed potent IL-18- and IL-12-inducing activities. IL-18 has been shown to correlate with chronic inflammation, so H. pylori LPS might be implicated in the chronic inflammatory responses induced by H. pylori. These results also indicated that H. pylori LPS can modulate the immune response: NF-κB activation through hTLR4/MD-2 was suppressed, whereas production of IL-18 and IL-12 was promoted.

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