Lentiviral-mediated interleukin-4 and interleukin-13 RNA interference decrease airway inflammation and hyperresponsiveness
Journal
Human Gene Therapy
Journal Volume
22
Journal Issue
5
Pages
577-586
Date Issued
2011
Author(s)
Abstract
Interleukin (IL)-4 and IL-13 are two key cytokines released from activated T helper type 2 (Th2) cells and strongly associated with asthma and allergic disease. We applied silencing of the IL-4 and IL-13 gene expression by RNA interference delivered by a lentiviral vector to evaluate the therapeutic role of IL-4 and IL13 short hairpin RNAs (shRNAs) in a murine model of asthma. Mice were sensitized with ovalbumin (OVA), and one treatment of IL-4 and IL-13 shRNA lentiviral vector (Lenti-si-IL-4 and Lenti-si-IL-13) was instilled intratracheally 48 hr before challenge. After three challenges of OVA antigen, mice were assessed for airway inflammation and hyperresponsiveness. With infection of Lenti-si-IL-4 and Lenti-si-IL-13 in EL-4 cells, both RNA and protein expressions of IL-4 and IL-13 were obviously abrogated. Furthermore, intratracheal instillation of Lenti-si-IL-4 and Lenti-si-IL-13 in OVA-immunized mice resulted in a strong inhibition of local IL-4 and IL-13 cytokine release. Treatment with Lenti-si-IL-4 and Lenti-si-IL-13 successfully alleviated OVA-induced airway eosinophilia and Th2 cell cytokine release. Finally, to determine airway hyperresponsiveness by enhanced pause and pulmonary resistance in noninvasive and invasive body plethysmography, we found that administration of Lenti-si- IL-4 and Lenti-si-IL-13 markedly decreased airway hyperresponsiveness in OVA-immunized mice. These results suggest that inhibition of IL-4 and IL-13 gene expression by shRNA lentiviral vector markedly inhibits antigeninduced airway inflammation and hyperresponsi eness in mice. ? 2011 Mary Ann Liebert, Inc.
SDGs
Other Subjects
interleukin 13; interleukin 4; lentivirus vector; ovalbumin; short hairpin RNA; airway hyperresponsiveness; airway inflammation; airway resistance; animal experiment; animal model; article; asthma; body plethysmography; controlled study; cytokine release; eosinophil; female; gene expression; gene silencing; human; human cell; immunization; lung resistance; mouse; nonhuman; protein expression; respiratory tract disease; RNA interference; sensitization; Th2 cell; Animals; Asthma; Gene Therapy; Genetic Vectors; Interleukin-13; Interleukin-4; Lentivirus; Mice; Ovalbumin; RNA Interference; RNA, Small Interfering; Murinae; Mus
Type
journal article