RNA interference against interleukin-5 attenuates airway inflammation and hyperresponsiveness in an asthma model.
Interleukin-5 (IL-5) accompanies the development of airway inflammation and hyperresponsiveness through the activation of eosinophils. Therefore, interference of IL-5 expression in lung tissue seems to be an accepted approach in asthma therapy. In this study, we designed a small interfering RNA (siRNA) to inhibit the expression of IL-5. The siRNAs against IL-5 were constructed in a lentivirus expressing system, and 1.5x10(6) IFU (inclusion-forming unit) lentiviruses were administered intratracheally to ovalbumin (OVA)-sensitized murine asthmatic models. Our results show that lentivirus-delivered siRNA against IL-5 efficiently inhibited the IL-5 messenger ribonucleic acid (mRNA) expression and significantly attenuated the inflammation in lung tissue. Significant decrease of eosinophils and inflammatory cells were found in peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, significant inhibition of airway hyperresponsiveness (AHR) was found in the mice treated with siRNA against IL-5. These observations demonstrate that siRNA delivered by means of the lentivirus system is possibly an efficacious therapeutic approach for asthma.
Chen
Shao-xing
SX
Hainan Medical College, Haikou, China.
Huang
Feng-ying
FY
Tan
Guang-hong
GH
Wang
Cai-chun
CC
Huang
Yong-hao
YH
Wang
Hua
H
Zhou
Song-lin
SL
Chen
Fan
F
Lin
Ying-ying
YY
Liu
Jun-bao
JB
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000276:immunology* / Q000517:prevention & control*; D012313:RNA / Q000627:therapeutic use*; D016896:Treatment Outcome
D015848:Interleukin-5; D012313:RNA