Suppression of cutaneous inflammation by intradermal gene delivery.
Biological effects of in vivo transfection of a potential anti-inflammatory gene, designated Sm16, cloned from the human parasite Schistosoma mansoni were analyzed in these studies. A single intradermal injection of a full-length cDNA of Sm16 resulted in the expression of Sm16 in the epidermis, dermis, skin migratory cells and skin-draining lymph nodes of mice for up to 7 days. Subsequently the anti-inflammatory effect of this gene expression was evaluated by inducing an inflammatory response in the skin of mice. These studies showed that Sm16 gene delivery resulted in a significant suppression of cutaneous inflammation as shown by a reduction in cutaneous edema, decrease in neutrophil infiltration, suppression of pro-inflammatory cytokine expression and down-regulation of ICAM-1 expression in the skin inflammatory site. Cells collected from the skin-draining lymph nodes showed reduced proliferation to mitogen. Multiple intradermal injection of Sm16 cDNA failed to induce any antibody response in mice for up to 8 weeks after initial injection. These findings suggest a potential for developing Sm16 gene delivery as a therapeutic agent for treating inflammatory skin disorders.
Rao
K V N
KV
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA.
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Y-X
YX
Ramaswamy
K
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D000818:Animals; D002455:Cell Division; D003587:Cytomegalovirus / Q000235:genetics; D018509:DNA, Helminth / Q000008:administration & dosage*; D003872:Dermatitis / Q000276:immunology / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D015801:Helminth Proteins / Q000235:genetics*; D007271:Injections, Intradermal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D012550:Schistosoma mansoni / Q000235:genetics*; D012867:Skin / Q000276:immunology
D018509:DNA, Helminth; D015801:Helminth Proteins; D008070:Lipopolysaccharides; C411707:SM16 protein, Schistosoma mansoni; D018799:Intercellular Adhesion Molecule-1