Effect of interleukin-5 receptor-alpha short hairpin RNA-expressing vector on bone marrow eosinophilopoiesis in asthmatic mice.
Bone marrow eosinophilopoiesis induced by interleukin (IL)-5 is a major contributor to eosinophilic airway inflammation in asthma. However,research on the use of IL-5 receptor alpha (IL-5Ralpha) as the target has seldom been reported. This study was undertaken to explore the effects of inhibition of IL-5Ralpha expression through an IL-5Ralpha short hairpin RNA-expressing vector on bone marrow eosinophilopoiesis and airway inflammation in an asthmatic mouse model. An effective plasmid vector was selected that could express short hairpin RNA targeted at IL-5Ralpha (P-IL-5Ralpha). An adenovirus vector (Ad) was then constructed that was inserted in an effective template sequence (Ad-IL-5Ralpha). An animal model of asthma was established by sensitizing and challenging Balb/c mice with ovalbumin. Animals were treated intravenously with Ad-IL-5Ra and changes in bone marrow eosinophilopoiesis and airway inflammation were detected in asthmatic mice. Investigators found that P-IL-5Ra-3 targeted at the sequence of CAG CTG CCT GGT TCG TCT T markedly suppressed IL-5Ralpha expression in B lymphoma cells in vitro. In addition, Ad-IL-5Ralpha could suppress IL-5Ralpha expression in murine bone marrow cells in vitro and in vivo, and it could significantly decrease IL-5-induced eosinophilia in cultured bone marrow cells. Additional studies indicated that intravenously injected Ad-IL-5Ralpha not only selectively reduced the number of eosinophils in the bone marrow, peripheral blood, and bronchoalveolar lavage fluid, it also relieved airway inflammation in asthmatic mice. Results reported here show that blocking of IL-5Ralpha expression through RNA interference can enhance effective treatment of asthma, and that bone marrow can be used as a key targeted organ in the treatment of asthmatic mice.
Mao
Hui
H
Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, PR China.
Wen
Fu-Qiang
FQ
Liu
Chun-Tao
CT
Liang
Zong-An
ZA
Wang
Zeng-Li
ZL
Yin
Kai-Sheng
KS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism* / Q000473:pathology; D015316:Genetic Therapy; D005822:Genetic Vectors; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D053666:Interleukin-5 Receptor alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics
D053666:Interleukin-5 Receptor alpha Subunit; D012313:RNA