Administration of Purified Alpha-1 Antitrypsin in Salt-Loaded Hypertensive 129Sv Mice Attenuates the Expression of Inflammatory Associated Proteins in the Kidney.

BACKGROUND: Alpha-1 antitrypsin (AAT) is a multifunctional protease inhibitor that has been shown to have anti-inflammatory properties in various diseases. AAT has been reported to protect against renal injury via anti-apoptotic, anti-fibrotic, and anti-inflammatory effects. However, its role in mitigating renal inflammation and reducing high blood pressure induced by salt-loading has never been studied. METHODS: In this study, we salt-loaded 129Sv mice to induce hypertension and then administered purified human AAT (hAAT) or the vehicle to investigate whether renal inflammation and associated inflammatory/signaling pathways are mitigated. RESULTS: Western blotting and densitometric analysis showed administration of hAAT attenuated protein expression of kidney injury molecule-1 (KIM1), CD93, CD36, and the toll-like receptor 2 and 4 (TLR-2/4) in kidney lysates. Similarly, protein expression of two key inflammatory transcription factors, signal transducer and activator of transcription 3 (STAT3) and NF-Kappa B were shown to be attenuated in the kidneys of 129Sv mice that received hAAT. Conversely, hAAT treatment upregulated the expression of heat shock protein 70 (HSP70) and immunohistochemistry confirmed these findings. CONCLUSIONS: Purified hAAT administration may be efficacious in mitigating renal inflammation associated with the development of hypertension from salt-loading, potentially through a mechanism involving the reduction of pro-inflammatory and injury-associated proteins.