Therapeutic effects of recombinant Salmonella typhimurium harboring CCL22 miRNA on atopic dermatitis-like skin in mice.

Abstract

Th-2-biased immune responses are known to play a key role in the pathogenesis of atopic dermatitis. In particular, the macrophage-derived chemokine CCL22 is directly implicated in Th-2-associated skin inflammatory reactions, and its levels are significantly elevated in serum and are correlated with disease severity in atopic dermatitis. In this study, we tested the development of genetic therapeutic options to treat atopic dermatitis using bacteria expressing miRNA. We constructed a recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The CCL22 gene was downregulated with CCL22 miRNA in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, interleukin-4 was inhibited and interferon-g was induced after treatments with ST-miRCCL22. Furthermore, CCL22 levels were suppressed in the atopic mice treated with ST-miRCCL22. These results suggest that ST-miRCCL22 may be an effective genetic agent for treating atopic dermatitis.

• Authors: Won Suck Yoon, Seung Seok Lee, Yang Seok Chae, Yong Keun Park
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 43 Issue 2 Pg. 63-70 (Feb 28 2011) ISSN: 2092-6413 [Electronic] United States
• PMID: 21187702 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL22
• Cytokines
• MicroRNAs
• Immunoglobulin E

Topics

• Animals
• Cell Line
• Chemokine CCL22 (genetics)
• Cytokines (blood)
• Dermatitis, Atopic (pathology)
• Disease Models, Animal
• Female
• Gene Expression Regulation (drug effects)
• Gene Silencing
• Immunoglobulin E (blood)
• Mice
• MicroRNAs (genetics, pharmacology)
• Organisms, Genetically Modified (genetics)
• Salmonella typhimurium (genetics, metabolism)
• Skin (drug effects, pathology)