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.
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.
Pritchard
D I
DI
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK. pazdp@gwmail.nottingham.ac.uk
Todd
I
I
Brown
A
A
Bycroft
B W
BW
Chhabra
S R
SR
Williams
P
P
Wood
P
P
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
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