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Tumor necrosis factor alpha small interfering RNA decreases herpes simplex virus-induced inflammation in a mouse model

Authors
 Bunsoon Choi  ;  Yunchung Hwang  ;  Hyuk Jae Kwon  ;  Eun-So Lee  ;  Kyung Sook Park  ;  Dongsik Bang  ;  Sungnack Lee  ;  Seonghyang Sohn 
Citation
 JOURNAL OF DERMATOLOGICAL SCIENCE, Vol.52(2) : 87-97, 2008 
Journal Title
 JOURNAL OF DERMATOLOGICAL SCIENCE 
ISSN
 0923-1811 
Issue Date
2008
MeSH
Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Behcet Syndrome/drug therapy* ; Behcet Syndrome/metabolism ; Behcet Syndrome/virology* ; Cells, Cultured ; Cytokines/metabolism ; Disease Models, Animal ; Etanercept ; Immunoglobulin G/pharmacology ; Immunoglobulin G/therapeutic use ; Infliximab ; Lipopolysaccharides/metabolism ; Macrophages/drug effects ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred ICR ; RNA, Small Interfering/pharmacology ; RNA, Small Interfering/therapeutic use* ; Receptors, Tumor Necrosis Factor/therapeutic use ; Simplexvirus/pathogenicity* ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/genetics* ; Tumor Necrosis Factor-alpha/metabolism
Keywords
TNF alpha ; SiRNA ; Herpes simplex virus ; Mouse model ; Behcet's disease ; In vivo
Abstract
BACKGROUND: Anti-TNFalpha antibodies have been used for treating inflammation in patients. But, more effective and safer drugs need to be developed for improved future therapeutic use. OBJECTIVES: To inhibit the expression of TNFalpha, we used small interfering RNAs (siRNAs) to reduce over expression of TNFalpha in vitro in cell cultures and in an in vivo Behcet's disease-like (BD) mouse model for amelioration of chronic inflammation. METHODS: TNFalpha siRNA was injected intraperitoneally twice with a 1-week interval. To compare the efficacy of TNFalpha siRNA versus an anti-TNFalpha antibody, Infliximab and Etanercept were administered to symptomatic mice with inflamed tissue. RESULTS: Intraperitoneal delivery of TNFalpha siRNA effectively decreased BD symptoms in 18 of 32 cases (56.3%). Scrambled siRNA treatment decreased BD symptoms in 2 of 19 cases (10.5%). Infliximab was effective in 11 of 27 cases (40.7%) and Etanercept was also effective in 9 of 25 cases (36.0%) at the end of the second week after treatment. TNFalpha siRNA reduced serum levels of TNFalpha (1.57 +/- 0.43pg/ml), compared to levels in mice not injected (84.02 +/- 24.59pg/ml) (p<0.01) or scramble injected (118.89 +/- 20.08pg/ml) (p<0.01). After single injection of TNFalpha siRNA, improvement of BD symptoms showed at 9 +/- 7th day on an average, contrary, in Infliximab injected group, improvement was apparent at 15 +/- 4th day after injection (p<0.05). CONCLUSION: We show that siRNAs can be employed to inhibit cytokine gene expression in an in vivo disease mouse model. This inhibition may, therefore, be attributed to the improvement of inflammatory symptoms.
Full Text
http://www.sciencedirect.com/science/article/pii/S0923181108001540
DOI
10.1016/j.jdermsci.2008.05.001
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Bang, Dong Sik(방동식)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107318
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