Recombinant osteopontin attenuates hyperoxia-induced acute lung injury through inhibiting nuclear fa

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Background Exposure of adult mice to more than 95% O2 produces a lethal injury by 72 hours.Nuclear factor kappa B (NF-κB) is a transcriptional factor that plays a key role in the modulation of cytokine networks during hyperoxia-induced acute lung injury (ALl).Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages.Studies have reported that exogenous OPN can maintain the integrity of the cerebral microvascular basement membrane and reduce brain damage through inhibiting NF-κB activities in the brain after subarachnoid hemorrhage.However,it is not clear whether OPN can reduce lung injury during ALl by inhibiting transcriptional signal pathways of NF-κB and consequent inhibition of infiammatory cytokines.Thus we examined the effects and mechanisms of recombinant OPN (r-OPN) on ALl.Methods Ninety-six mice were randomly divided into phosphate buffered saline (PBS) and r-OPN groups.Mice were put in an oxygen chamber (>95% O2) and assessed for lung injury at 24,48,and 72 hours.Expressions of NF-κB,matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9),and tissue inhibitors of MMP-2 and MMP-9 (TIMP-1,TIMP-2) mRNA in lungs were examined with RT-PCR.Expression and distribution of NF-κB protein in lungs were measured with immunohistochemistry.Results Exposure to hyperoxia for 72 hours induced more severe lung injury in the PBS group compared with the r-OPN group.Expression of NF-κB mRNA in the PBS group exposed to hyperoxia for 48 and 72 hours was significantly higher than the r-OPN group (P <0.05).With 72-hour exposure,expression of TIMP-1 mRNA in the r-OPN group was significantly higher than that of the PBS group (P <0.05).Expression of TIMP-2 mRNA in the r-OPN group at 48 and 72 hours was significantly higher than those in the PBS group (P <0.05).After 72-hour exposure,expression of NF-κB protein in airway epithelium in the PBS group was significantly higher than that in the r-OPN group (P <0.05).Conclusion r-OPN can inhibit the release and activation of MMPs through inhibition of the expression of NF-κB and promotion of the expression of TIMPs,and alleviate hyperoxia-induced ALl.
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