title: Antibacterial activity of a novel synthetic progesterone species carrying a linoleic acid molecule against Helicobacter pylori and the hormonal effect of its steroid on a murine macrophage-like cell line.
abstract: Helicobacter pylori, a pathogen responsible for gastric and duodenal diseases, absorbs various steroid compounds into the cell membrane even though some are toxic to this bacterium. An earlier study by our group has demonstrated that progesterone is bactericidal to H. pylori. In this study, we newly synthesized a steroid compound, 17α-hydroxyprogesterone linoleic acid ester (17hPL), to examine antibacterial activity against H. pylori. As expected, 17hPL acted as a bactericidal agent to H. pylori and had no effect on the survival of other common bacterial species. This steroidal substance interacted with phosphatidylethanolamine (PE) on the outer membrane of H. pylori to induce the release of PE from the bacterial cell membrane and to ultimately lyse the bacterial cells. One of the hormonal effects of progesterone is the inhibition of nitric oxide (NO) production from mouse macrophages activated by lipopolysaccharide (LPS). We therefore examined the inhibition effect of 17hPL on the NO production of RAW 264.7 cells, a murine macrophage-like cell line, stimulated with LPS and demonstrated that 17hPL is relatively weaker in its capability to inhibit NO production in LPS-activated cells than progesterone. These results suggest the possibility that 17hPL could be an oral medicine for selectively treating patients infected with H. pylori.
authors.affiliation: Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
authors.forename: Avarzed
authors.initials: A
authors.lastname: Amgalanbaatar
authors.affiliation: Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan. Electronic address: shimo@jichi.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shimomura
authors.affiliation: Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hosoda
authors.affiliation: Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmacology, Okayama University, 1-1-1, Tsushimanaka, Kita-ku, Okayama-shi, Okayama 700-8530, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokota
authors.affiliation: Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirai
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001433:Bacteriolysis / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011374:Progesterone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: C587261:17-hydroxyprogesterone linoleic acid ester; D000900:Anti-Bacterial Agents; D010714:Phosphatidylethanolamines; D009569:Nitric Oxide; C483858:phosphatidylethanolamine; D011374:Progesterone
keywords: 17hP4; 17hPC; 17hpl; 17α-Hydroxyprogesterone; 17α-Hydroxyprogesterone caproate; 17α-Hydroxyprogesterone linoleic acid ester; 17α-hydroxyprogesterone; 17α-hydroxyprogesterone caproic acid ester; 17α-hydroxyprogesterone linoleic acid ester; 2,6-di-O-methyl-β-cyclodextrin; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; CGs; FC; Helicobacter pylori; LPS; MTT; PE; PG-CL; PPLO; Preg4; Progesterone; cholesteryl glucosides; dMβCD; free cholesterol; lipopolysaccharide; phosphatidylethanolamine; phosphatidylglycerol-cardiolipin; pleuropneumonia-like organisms; progesterone