title: Alleviation of insulitis and moderation of diabetes in NOD mice following treatment with a synthetic Pseudomonas aeruginosa signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone.
abstract: Quorum sensing signal molecules (QSSMs) from the bacterium Pseudomonas aeruginosa control bacterial population density and the expression of virulence determinants. Coincidentally, and possibly to allow this pathogen to gain a foothold in the human body, certain signal molecules also downregulate immunological responses in an apparently T-helper 1-selective manner, which would suggest their application as therapeutics to some autoimmune diseases. In the present paper, experiments are described that indicate that one particular signal molecule, a synthetic N-(3-oxododecanoyl)-L-homoserine lactone, can be used to alleviate insulitis and diabetes in non-obese diabetic (NOD) mice, suggesting that bacterial signal molecules may represent a novel source of immune modulatory compounds for the treatment of type 1 diabetes, which afflicts more than 2 million individuals in Europe and North America.
authors.affiliation: School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK. pazdp@gwmail.nottingham.ac.uk
authors.forename: D I
authors.initials: DI
authors.lastname: Pritchard
authors.forename: I
authors.initials: I
authors.lastname: Todd
authors.forename: A
authors.initials: A
authors.lastname: Brown
authors.forename: B W
authors.initials: BW
authors.lastname: Bycroft
authors.forename: S R
authors.initials: SR
authors.lastname: Chhabra
authors.forename: P
authors.initials: P
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Wood
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003920:Diabetes Mellitus / Q000517:prevention & control*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D010182:Pancreatic Diseases / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa
chemical_list: D000276:Adjuvants, Immunologic; C109860:N-(3-oxododecanoyl)homoserine lactone; D006714:Homoserine; C030654:N-(3-oxohexanoyl)-3-aminodihydro-2(3H)-furanone; D015107:4-Butyrolactone; D004121:Dimethyl Sulfoxide