Deficiency of the Transcription Factor NR4A1 Enhances Bacterial Clearance and Prevents Lung Injury During Escherichia Coli Pneumonia

This study aims to explore the role of NR4A1 in Escherichia coli (E. coli) pneumonia. Methods: Alveolar macrophages (AMs) were isolated from wild-type (WT) and NR4A1 knock out (Nr4a1−/−) mice, and the NR4A1 expression and phagocytic capacity against E. coli were measured in vitro. WT and Nr4a1−/− mice were subjected to E. coli or sham pneumonia. Bacterial load, lung injury severity, inflammatory cell infiltration, and cytokines were assessed at 0, 4, and 18 h after surgery. Survival rates within 48 h were evaluated in WT and Nr4a1−/− mice. In addition, NR4A1 antagonist (DIM-C-pPhCO2Me) was also used to confirm the role of NR4A1 in vivo and ex vivo. Results: NR4A1 was rapidly induced in AMs at 15 min after E. coli stimulation. Compared with untreated WT AMs, NR4A1 deficiency and DIM-C-pPhCO2Me treatment showed an enhanced phagocytic function (47.72 ± 0.74% vs. 62.3 ± 0.9%, P 
Source: Shock - Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research