Exp Mol Med.  2011 Feb;43(2):63-70. 10.3858/emm.2011.43.2.008.

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

• Yoon WS
• Lee SS
• Chae YS
• Park YK

• KMID: 1097263
• DOI: http://doi.org/10.3858/emm.2011.43.2.008

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-gamma 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.

Keyword

biological therapy; chemokine CCL22; dermatitis, atopic; immunotherapy; RNA interference; Salmonella typhimurium

MeSH Terms

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