Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction.

Abstract

Abnormal lung inflammation and oxidant burden are associated with a significant reduction in histone deacetylase 2 (HDAC2) abundance and steroid resistance. We hypothesized that Nrf2 regulates steroid sensitivity via HDAC2 in response to inflammation in mouse lung. Furthermore, HDAC2 deficiency leads to steroid resistance in attenuating lung inflammatory response, which may be due to oxidant/antioxidant imbalance. Loss of antioxidant transcription factor Nrf2 resulted in decreased HDAC2 level in lung, and increased inflammatory lung response which was not reversed by steroid. Thus, steroid resistance or inability of steroids to control lung inflammatory response is dependent on Nrf2-HDAC2 axis. These findings have implications in steroid resistance, particularly during the conditions of oxidative stress when the lungs are more susceptible to inflammatory response, which is seen in patients with chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, and inflammatory bowel disease.

• Authors: David Adenuga, Samuel Caito, Hongwei Yao, Isaac K Sundar, Jae-Woong Hwang, Sangwoon Chung, Irfan Rahman
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 403 Issue 3-4 Pg. 452-6 (Dec 17 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 21094147 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Glucocorticoids
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Budesonide
• Hdac2 protein, mouse
• Histone Deacetylase 2

Topics

• Animals
• Budesonide (therapeutic use)
• Drug Resistance (genetics)
• Glucocorticoids (therapeutic use)
• Histone Deacetylase 2 (genetics, metabolism)
• Mice
• Mice, Knockout
• NF-E2-Related Factor 2 (genetics)
• Pneumonia (drug therapy, enzymology)