An oligodeoxynucleotide capable of lessening acute lung inflammatory injury in mice infected by influenza virus.
Infection of influenza virus could induce acute lung inflammatory injury (ALII) that was at least partially caused by excessive innate immune responses. To study whether down-regulating Toll-like receptor (TLR)-mediated innate immune response could lessen influenza virus-induced ALII, a microsatellite DNA mimicking oligodeoxynucleotide (MS ODN), named as SAT05f capable of inhibiting TLR7/9-activation in vitro, was used to treat mice infected with FM1 virus. In parallel, two MS ODNs confirmed with less or no in vitro activities, named as MS19 and MS33, were used as controls. Unexpectedly, SAT05f failed to lessen ALII in the mice, whereas MS19 significantly inhibited the weight loss and displayed dramatic effect on lessening the ALII by reducing consolidation, hemorrhage, intra-alveolar edema and neutrophils infiltration in lungs of the mice. Meanwhile, MS19 could decrease the mortality of influenza virus infected mice and down-regulate TNF-α production in their lungs. The data suggest that MS19 might display its therapeutic role on ALII induced by influenza virus by reducing over-production of TNF-α.
Department of Molecular Biology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.
Mingli
M
Fang
Min
M
Wan
Sheng
S
Guo
Ran
R
Sun
Ming
M
Yang
TieSuo
T
Zhao
Youyou
Y
Yan
Yongsheng
Y
Zhang
Wenhui
W
Huang
Xiuli
X
Wu
Yongli
Y
Yu
Liying
L
Wang
Shucheng
S
Hua
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D000818:Animals; D005260:Female; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D018895:Microsatellite Repeats; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000627:therapeutic use*; D009976:Orthomyxoviridae Infections / Q000150:complications*; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C569331:MS19 oligodeoxynucleotide; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; C561797:SAT05f; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha