Short hairpin RNAs against eotaxin or interleukin-5 decrease airway eosinophilia and hyper-responsiveness in a murine model of asthma.
BACKGROUND
Eosinophilia plays the major role in the pathogenesis of asthma and correlates with the up-regulation of eotaxin, which, together with interleukin (IL)-5, is important for differentiation, chemo-attraction, degranulation, and survival of eosinophils in local tissue. In a previous study, we found that administration of lentivirus-delivered short hairpin RNA (shRNA) to suppress the expression of IL-5 inhibited airway inflammation. The present study aimed to investigate the role of eotaxin shRNA and the synergistic effect of eotaxin and IL-5 shRNAs on airway inflammation in an ovalbumin (OVA)-induced murine model of asthma.


METHODS
Lentivirus-delivered shRNAs were used to suppress the expression of eotaxin and/or IL-5 in local tissue in an OVA-induced murine asthma model.


RESULTS
Intra-tracheal administration of lentivirus containing eotaxin shRNA expressing cassette (eoSEC3.3) efficiently moderated the characteristics of asthma, including airway hyper-responsiveness, cellular infiltration of lung tissues, and eotaxin and IL-5 levels in bronchio-alveolar lavage fluid. Administration of lentiviruses expressing IL-5 or eotaxin shRNAs (IL5SEC4 + eoSEC3.3) also moderated the symptoms of asthma in a mouse model.


CONCLUSIONS
Local delivery of lentiviruses expressing IL-5 and eotaxin shRNAs provides a potential tool in moderating airway inflammation and also has the potential for developing clinical therapy based on the application of shRNAs of chemokines and cytokines involved in T helper 2 cell inflammation and eosinophilia.
Huang
Hsin-Ying
HY
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lee
Chen-Chen
CC
Chiang
Bor-Luen
BL
D000818:Animals; D001249:Asthma / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D019742:Chemokines, CC / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000628:therapy*; D034622:RNA Interference; D022661:RNA, Untranslated / Q000008:administration & dosage*
D019742:Chemokines, CC; D015848:Interleukin-5; D022661:RNA, Untranslated