Protective actions of aspirin-triggered (17R) resolvin D1 and its analogue, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester, in C5a-dependent IgG immune complex-induced inflammation and lung injury.

Abstract

Increasing evidence suggests that the novel anti-inflammatory and proresolving mediators such as the resolvins play an important role during inflammation. However, the functions of these lipid mediators in immune complex-induced lung injury remain unknown. In this study, we determined the role of aspirin-triggered resolvin D1 (AT-RvD1) and its metabolically stable analog, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester (p-RvD1), in IgG immune complex-induced inflammatory responses in myeloid cells and injury in the lung. We show that lung vascular permeability in the AT-RvD1- or p-RvD1-treated mice was significantly reduced when compared with values in mice receiving control vesicle during the injury. Furthermore, i.v. administration of either AT-RvD1 or p-RvD1 caused significant decreases in the bronchoalveolar lavage fluid contents of neutrophils, inflammatory cytokines, and chemokines. Of interest, AT-RvD1 or p-RvD1 significantly reduced bronchoalveolar lavage fluid complement C5a level. By EMSA, we demonstrate that IgG immune complex-induced activation of NF-κB and C/EBPβ transcription factors in the lung was significantly inhibited by AT-RvD1 and p-RvD1. Moreover, AT-RvD1 dramatically mitigates IgG immune complex-induced NF-κB and C/EBP activity in alveolar macrophages. Also, secretion of TNF-α, IL-6, keratinocyte cell-derived chemokine, and MIP-1α from IgG immune complex-stimulated alveolar macrophages or neutrophils was significantly decreased by AT-RvD1. These results suggest a new approach to the blocking of immune complex-induced inflammation.

• Authors: Huifang Tang, Yanlan Liu, Chunguang Yan, Nicos A Petasis, Charles N Serhan, Hongwei Gao
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 7 Pg. 3769-78 (Oct 01 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 25172497 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antigen-Antibody Complex
• CCAAT-Enhancer-Binding Proteins
• Ccl3 protein, mouse
• Chemokine CCL3
• Cytokines
• Immunoglobulin G
• NF-kappa B
• resolvin D1
• Docosahexaenoic Acids
• Complement C5a
• Aspirin

Topics

• Acute Lung Injury (chemically induced, immunology, pathology, prevention & control)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Antigen-Antibody Complex (immunology)
• Aspirin (pharmacology)
• Bronchoalveolar Lavage Fluid (immunology)
• CCAAT-Enhancer-Binding Proteins (immunology)
• Cell Line
• Chemokine CCL3 (immunology)
• Complement C5a (immunology)
• Cytokines (immunology)
• Docosahexaenoic Acids
• Immunoglobulin G (immunology)
• Macrophages, Alveolar (immunology, pathology)
• Mice
• NF-kappa B (immunology)
• Neutrophils (immunology, pathology)
• Pneumonia (chemically induced, immunology, pathology, prevention & control)