Locally administered lentivirus-mediated siRNA inhibits wear debris-induced inflammation in murine air pouch model.
Lentivirus(LV)-mediated small interfering RNA (siRNA) targeting tumor necrosis factor-alpha (TNF-alpha) was locally administered into the air pouch of mice to inhibit inflammation induced by titanium alloy particles. The lentiviral vector expressed green fluorescent protein (GFP) as a reporter gene. Down-regulation of TNF-alpha in pouch area was confirmed by real-time PCR and ELISA, resulting in significantly decreased local inflammatory responses (P < 0.01). This approach was proven safe by localized GFP fluorescence and invariant TNF-alpha expression in peripheral blood, liver, spleen, kidney, lung and brain of mouse. In conclusion, locally administered siRNA provides an effective and safe method for inhibiting particle-induced inflammation.
Peng
Xiaochun
X
Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, China.
Zhang
Xianlong
X
Zeng
Bingfang
B
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics*; D008163:Luminescent Measurements / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014025:Titanium / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins; D014025:Titanium