15-epi-Lipoxin A 4 , Resolvin D2, and Resolvin D3 Induce NF-κB Regulators in Bacterial Pneumonia

• Published in: The Journal of immunology (1950) Vol. 200; no. 8; p. 2757
• Main Authors: Sham, Ho Pan, Walker, Katherine H, Abdulnour, Raja-Elie E, Krishnamoorthy, Nandini, Douda, David N, Norris, Paul C, Barkas, Ioanna, Benito-Figueroa, Sarah, Colby, Jennifer K, Serhan, Charles N, Levy, Bruce D
• Format: Journal Article
• Language: English
• Published: United States 15.04.2018
• Subjects: Animals; Cell Line; Docosahexaenoic Acids - immunology; Docosahexaenoic Acids - metabolism; Fatty Acids, Unsaturated - immunology; Fatty Acids, Unsaturated - metabolism; Humans; Inflammation - immunology; Inflammation - metabolism; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Lipoxins - immunology; Lipoxins - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B - immunology; Pneumonia, Bacterial - immunology; Pneumonia, Bacterial - metabolism; Receptors, Interleukin-1 - agonists; Tumor Necrosis Factor alpha-Induced Protein 3 - metabolism
• ISSN: 1550-6606

Specialized proresolving mediators (SPMs) decrease NF-κB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-κB regulation by SPMs remain to be determined. In this study, after LPS challenge, the SPMs 15-epi-lipoxin A (15-epi-LXA ), resolvin D1, resolvin D2, resolvin D3, and 17-epi-resolvin D1 were produced in vivo in murine lungs. In LPS-activated human bronchial epithelial cells, select SPMs increased expression of the NF-κB regulators A20 and single Ig IL-1R-related molecule (SIGIRR). Of interest, 15-epi-LXA induced and in an lipoxin A receptor/formyl peptide receptor 2 (ALX/FPR2) receptor-dependent manner in epithelial cells and in murine pneumonia. This SPM regulated NF-κB-induced cytokines to decrease pathogen-mediated inflammation. In addition to dampening lung inflammation, surprisingly, 15-epi-LXA also enhanced pathogen clearance with increased antimicrobial peptide expression. Taken together, to our knowledge these results are the first to identify endogenous agonists for A20 and SIGIRR expression to regulate NF-κB activity and to establish mechanisms for NF-κB regulation by SPMs for pneumonia resolution.