title: Innate immunomodulation by lipophilic termini of lipopolysaccharide; synthesis of lipid As from Porphyromonas gingivalis and other bacteria and their immunomodulative responses.
abstract: Synthetic studies of lipid A and LPS partial structures have been performed to investigate the relationship between structures and functions of LPS. Recent studies have suggested several pathological implications of LPS from parasitic bacteria due to its influence on the host immune responses. To address this issue, we established an efficient synthetic strategy that is widely applicable to the synthesis of various lipid As by using a key disaccharide intermediate with selectively cleavable protecting groups. Porphyromonas gingivalis and Helicobacter pylori lipid As were synthesized and their biological activities were evaluated. All synthetic lipid As did not induce strong inflammatory responses: some are very weak cytokine inducers and others are antagonistic in IL-6 and IL-8 induction with E. coli LPS. On the other hand, P. gingivalis lipid As showed potent IL-18 inducing activity. Since IL-18 has been shown to correlate with chronic inflammation, P. gingivalis LPS may be implicated in the chronic inflammatory responses.
authors: Department of Chemistry, Graduate School of Science, Osaka University, Machikaneyama 1-1, Toyonaka, Osaka 560-0043, Japan. yukarif@chem.sci.osaka-u.ac.jp
authors: Yukari
authors: Y
authors: Fujimoto
authors: Atsushi
authors: A
authors: Shimoyama
authors: Akinori
authors: A
authors: Saeki
authors: Naohiro
authors: N
authors: Kitayama
authors: Chika
authors: C
authors: Kasamatsu
authors: Hiroko
authors: H
authors: Tsutsui
authors: Koichi
authors: K
authors: Fukase
mesh_terms: D016866:Bacteroidaceae Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology; D060326:Chemistry Techniques, Synthetic / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D016481:Helicobacter Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D056747:Immunomodulation / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D008050:Lipid A / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008956:Models, Chemical; D015394:Molecular Structure; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D008050:Lipid A; D008070:Lipopolysaccharides