2-Methoxyestradiol protects against IgG immune complex-induced acute lung injury by blocking NF-κB and CCAAT/enhancer-binding protein β activities.

Abstract

Increasing evidences indicate that 2-Methoxyestradiol (2ME2) plays an essential role in protecting against inflammatory responses. However, its effect on IgG immune complex (IC)-induced acute lung injury (ALI) remains enigmatic. In the study, by using i.p. administration of 2ME2, we evaluated its influence on IgG IC-induced pulmonary injury in mice. We found that during IgG IC-induced ALI, mice treated by 2ME2 displayed a substantial decrease in vascular permeability and neutrophil influx (represented by myeloperoxidase activity) when compared with their counterparts receiving vehicle treatment. Furthermore, 2ME2 treatment significantly decreased pro-inflammatory mediator production and inflammatory cell, especially neutrophil accumulation in bronchoalveolar lavage fluids (BALFs) upon IgG IC stimulation. In vitro, IgG IC-triggered inflammatory mediator production was markedly down-regulated by 2ME2 in macrophages. Moreover, we verified that the activation of the transcription factors, NF-κB and CCAAT/enhancer-binding protein (C/EBP) β, were inhibited by 2ME2 in IgG IC-challenged macrophages. We demonstrated that alleviation of NF-κB-dependent transcription might be associated with reduced phosphorylation of NF-κB p65, and reduction of C/EBP activation was directly linked to its expression. In addition, we discovered that IgG IC-stimulated phosphorylation of both p38 MAPK and ERK1/2 was alleviated by 2ME2. These data indicated a novel strategy for blockade of IgG IC-induced inflammatory activities.

• Authors: Chunguang Yan, Yanfei Shen, Qiqing Sun, Dong Yuan, Huifang Tang, Hongwei Gao
• Journal: Molecular immunology (Mol Immunol) Vol. 85 Pg. 89-99 (05 2017) ISSN: 1872-9142 [Electronic] England
• PMID: 28214650 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Antigen-Antibody Complex
• CCAAT-Enhancer-Binding Protein-beta
• Immunoglobulin G
• NF-kappa B
• Estradiol
• 2-Methoxyestradiol

Topics

• 2-Methoxyestradiol
• Acute Lung Injury (immunology, metabolism)
• Animals
• Antigen-Antibody Complex (toxicity)
• Blotting, Western
• CCAAT-Enhancer-Binding Protein-beta (drug effects, immunology, metabolism)
• Disease Models, Animal
• Estradiol (analogs & derivatives, pharmacology)
• Immunoglobulin G (toxicity)
• Macrophages, Alveolar (drug effects, immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (drug effects, immunology, metabolism)
• Real-Time Polymerase Chain Reaction