Small interfering RNA against interleukin-5 decreases airway eosinophilia and hyper-responsiveness.
Interleukin-5 (IL-5) has been suggested to be involved in the development of airway hyper-responsiveness (AHR). Both clinical and experimental investigations have shown strong correlation between the presence of eosinophils and AHR. In this study, we used small interfering RNA (siRNA) as an approach to inhibiting the expression of IL-5 and reducing AHR. siRNAs targeting IL-5 were characterized in vitro, and siRNA-expressing lentiviruses were administered intratracheally to OVA-sensitized BALB/c mice. AHR, cytokine levels, serum levels of OVA-specific antibodies and infiltration of inflammatory cells were analyzed to investigate the effects of siRNA in an OVA-induced murine model of asthma. Lentivirus-delivered siRNA targeting IL-5 efficiently moderated the characteristics of asthma, including AHR, cellular infiltration of lung tissues, eotaxin levels in the bronchoalveolar lavage fluid and IL-5 mRNA levels in lungs in the mouse model of asthma. However, there was no effect on OVA-specific IgE level. These data demonstrate that siRNA delivered by the lentiviral system is an efficacious therapeutic strategy for asthma.
Huang
H-Y
HY
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lee
C-C
CC
Chiang
B-L
BL
D020121:5' Untranslated Regions; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D045744:Cell Line, Tumor; D054413:Chemokine CCL11 / Q000032:analysis; D015316:Genetic Therapy / Q000379:methods*; D015848:Interleukin-5 / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020121:5' Untranslated Regions; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D015848:Interleukin-5; D034741:RNA, Small Interfering; D010047:Ovalbumin