title: VGX-1027 modulates genes involved in lipopolysaccharide-induced Toll-like receptor 4 activation and in a murine model of systemic lupus erythematosus.
abstract: VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid] is a small molecule compound with immunomodulatory properties, which favourably influences the development of immuno-inflammatory and autoimmune diseases in different animal models such as type 1 diabetes mellitus, pleurisy, rheumatoid arthritis and inflammatory bowel disease. However, the precise mechanism of action of VGX-1027 remains to be ascertained. With this aim, we have studied the immunomodulatory effects of VGX-1027 in vitro, using a genome-wide oligonucleotide microarray approach, and in vivo, using the NZB/NZW F1 model of systemic lupus erythematosus. Microarray data revealed that the administration of VGX-1027 profoundly affected the immune response to exogenous antigens, by modulating the expression of genes that are primarily involved in antigen processing and presentation as well as genes that regulate immune activation. When administered in vivo VGX-1027 ameliorated the course of the disease in the NZB/NZW F1 mice, which correlated with higher per cent survival and improved clinical and histopathological signs. The data presented herein support the theory that VGX-1027 modulates immunity, probably by inhibiting inflammatory antigen presentation and so limiting immune cell expansion.
authors: Department of Bio-Medical Sciences, University of Catania, Catania, Italy.
authors: Paolo
authors: P
authors: Fagone
authors: Karuppiah
authors: K
authors: Muthumani
authors: Katia
authors: K
authors: Mangano
authors: Gaetano
authors: G
authors: Magro
authors: Pier Luigi
authors: PL
authors: Meroni
authors: Joseph J
authors: JJ
authors: Kim
authors: Niranjan Y
authors: NY
authors: Sardesai
authors: David B
authors: DB
authors: Weiner
authors: Ferdinando
authors: F
authors: Nicoletti
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: C518641:3-phenyl-4,5-dihydro-5-isoxazole acetic acid; D000085:Acetates; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D010080:Oxazoles; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: autoimmunity; bioinformatics; cell activation