Erythromycin Regulates Cigarette Smoke-Induced Proinflammatory Mediator Release Through Sirtuin 1-Nuclear Factor κB Axis in Macrophages and Mice Lungs.

Abstract

BACKGROUND:

Macrolides have anti-inflammatory and antioxidative stress function, but their pharmacological regulation remains unclear. Sirtuin 1 (SIRT1) is redox-sensitive protein belongs to class III histone/protein deacetylases, SIRT1 regulates the acetylation/expression of nuclear factor κB (NF-κB) and is involved in the airway inflammation of chronic obstructive pulmonary disease.

OBJECTIVES:

The present study was designed to examine the effects of erythromycin (EM) on the SIRT1-NF-κB axis and NF-κB-dependent proinflammatory cytokines.

METHODS:

Human macrophages were preincubated with EM and then treated with cigarette smoke extract (CSE). The mice were treated by injecting drugs to gastric with EM before cigarette smoke exposure. Reactive oxygen species (ROS) released by treated human macrophages were detected using flow cytometry. The expression of SIRT1 and NF-κB was analyzed by western blotting. SIRT1 and the RelA/p65 subunits of NF-κB interaction were detected by coimmunoprecipitation. We found that EM suppressed CSE-induced ROS released in human macrophages, which coincided with increases in SIRT1 protein expression in the macrophages and lungs of mice, resulting in suppressed -NF-κB acetylation and expression correlated with a reduction of inflammatory mediators.

CONCLUSION:

These findings suggest that EM increased SIRT1, leading to acetylation/expression of NF-κB, and thereby decreasing cigarette smoke-driven NF-κB-dependent proinflammatory cytokine.

• Authors: Nan Ma, Ting-Ting Deng, Qin Wang, Zhou-Ling Luo, Cai-Feng Zhu, Ju-Feng Qiu, Xiao-Juan Tang, Mei Huang, Jing Bai, Zhi-Yi He, Xiao-Ning Zhong, Mei-Hua Li
• Journal: Pathobiology : journal of immunopathology, molecular and cellular biology (Pathobiology) Vol. 86 Issue 5-6 Pg. 237-247 ( 2019) ISSN: 1423-0291 [Electronic] Switzerland
• PMID: 31242482 (Publication Type: Journal Article)
• Copyright: © 2019 S. Karger AG, Basel.

Chemical References

• NF-kappa B
• Reactive Oxygen Species
• Smoke
• Erythromycin
• Sirtuin 1

Topics

• Animals
• Cells, Cultured
• Erythromycin (pharmacology)
• Humans
• Inflammation
• Lung (drug effects, immunology)
• Macrophages (drug effects)
• Male
• Mice
• Mice, Inbred BALB C
• NF-kappa B (genetics, immunology)
• Reactive Oxygen Species (metabolism)
• Sirtuin 1 (genetics, immunology)
• Smoke (adverse effects)
• Specific Pathogen-Free Organisms
• Tobacco Products (adverse effects)