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

Shock
Ping CuiXiangming Fang

Abstract

Bacterial pneumonia is one of the most common diagnoses and a leading cause of death in the intensive care unit. NR4A1 is an early response gene that has been identified as a vital regulator of immune and inflammatory responses. This study aims to explore the role of NR4A1 in Escherichia coli (E. coli) pneumonia. 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. 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 < 0.001; 11.79 ± 1.21% vs. 30.08 ± 0.79%, P < 0.001, respectively) at 30 min after the E. coli challenge in vitro. NR4A1 deficiency significantly improved the...Continue Reading

References

Jun 21, 2005·The Journal of Biological Chemistry·Liming PeiPeter Tontonoz
Jul 12, 2005·Annual Review of Biomedical Engineering·Scott I Simon, Chad E Green
Jul 29, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Peter I BontaCarlie J M de Vries
Aug 16, 2008·Shock·José C Alves-FilhoFernando Q Cunha
Dec 3, 2009·JAMA : the Journal of the American Medical Association·Jean-Louis VincentUNKNOWN EPIC II Group of Investigators
May 14, 2010·The New England Journal of Medicine·Anton Y Peleg, David C Hooper
May 3, 2011·American Journal of Respiratory Cell and Molecular Biology·Gustavo Matute-BelloUNKNOWN Acute Lung Injury in Animals Study Group
Dec 24, 2011·Circulation Research·Anouk A J HamersCarlie J M de Vries
Jul 31, 2012·Current Opinion in Immunology·Taylor Eddens, Jay K Kolls
Jan 16, 2013·The Journal of Pharmacology and Experimental Therapeutics·Briana R De MirandaRonald B Tjalkens
Oct 30, 2013·Infection and Immunity·Anouk A J HamersCornelis van 't Veer
Jan 22, 2014·Nature Reviews. Immunology·Tracy Hussell, Thomas J Bell
Oct 23, 2014·The New England Journal of Medicine·Daniel M Musher, Anna R Thorner
Nov 8, 2014·International Review of Cell and Molecular Biology·Gengming NiuGuangjian Huang
Jan 13, 2015·Nature Medicine·Katrin Palumbo-ZerrJörg H W Distler
Jul 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kondababu KurakulaCarlie J M de Vries
Sep 2, 2015·European Respiratory Review : an Official Journal of the European Respiratory Society·Manminder KaurTracy Hussell
Mar 18, 2016·Immunity·Siamon Gordon
Jan 6, 2017·Expert Opinion on Therapeutic Targets·Ricardo Rodríguez-CalvoManuel Vázquez-Carrera
May 17, 2017·Frontiers in Cellular and Infection Microbiology·Roger D Pechous

❮ Previous
Next ❯

Citations

May 16, 2019·Shock·Max Brenner, Ping Wang
Jun 7, 2019·Pharmacological Reports : PR·Michael KozlowskiKrzysztof Bryniarski
Dec 24, 2021·Frontiers in Cellular and Infection Microbiology·Valerie P O'BrienNicole M Gilbert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Pneumonia (ASM)

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Bacterial Pneumonia

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.