VGX‐1027 modulates genes involved in lipopolysaccharide‐induced Toll‐like receptor 4 activation and in a murine model of systemic lupus erythematosus. Issue 4 (August 2014)

• Record Type: Journal Article
• Authors: Fagone, Paolo; Muthumani, Karuppiah; Mangano, Katia; Magro, Gaetano; Meroni, Pier Luigi; Kim, Joseph J.; Sardesai, Niranjan Y.; Weiner, David B.; Nicoletti, Ferdinando
• Is Part Of: Immunology. Volume 142:Issue 4(2014:Aug.)
• Page Start: 594
• Page End: 602
• Publication Date: 2014-08
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12267
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12267-abs-0001"> <title>Summary</title> <p>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 <italic>in vitro</italic>, using a genome‐wide oligonucleotide microarray approach, and <italic>in vivo</italic>, 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 <italic>in vivo </italic>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.</p> </abstract>