CPG-52364 targeted TLR9 regulate lung injury induced by inflammation reaction resulting from elderly hip fracture caused mtDNA release

Abstract

Xiao Yang, Guangpeng Ou, Bei Li, Zhen Liu, Di Zhou, Li Gan

Background: Acute lung injury (ALI) after elderly hip fracture is the serious and fatal complication, it is associated with inflammation induced by mtDNA release activates TLR9/NF-KB pathway after trauma. Inhibiting TLR9 pathway activation can alleviate the systemic inflammation and ALI after elderly hip fracture. In the first part of our study, we investigate the effect of the TLR9 inhibitor (CPG-52364) in the pathological process of inflammation and ALI after elderly hip fracture. In the second part of our study, we investigate the effect of CPG-52364 in the pathological process of inflammation and ALI induced by mtDNA. Material and Methods- In the first part of our study, the elderly rats received hip fracture operations and CPG-52364 managed. The degree of lung injury and inflammation were evaluated, TLR9/ NF-KB were determined using Western blot, and mtDNA were analyzed by fluorescent quantitative polymerase chain reaction. In the second part of our study, the elderly rats received mtDNA injection and CPG-52364 managed, the specimens were collected and detected as the first part.

Results: Both hip fracture and mtDNA injection can cause significant cytokines (IL-6 and IL-10) release, TLR9 and NFKBp65 expression, and lung injury in the elderly rats. CPG-52364 can effectively down-regulate the expression of the above pathological indicators.

Conclusion: These results suggest that the CPG-52364 can down-regulate the TLR9/NF-KB pathway to control the inflammation and ALI induced by mtDNA release after elderly hip fracture.

PDF