15-epi-lipoxin A4, resolvin D2, and resolvin D3 induce NF-kB regulators in bacterial pneumonia

Ho Pan Sham, Katherine H. Walker, Raja Elie E. Abdulnour, Nandini Krishnamoorthy, David N. Douda, Paul C. Norris, Ioanna Barkas, Sarah Benito-Figueroa, Jennifer K Long Colby, Charles N. Serhan, Bruce D. Levy

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Abstract

Specialized proresolving mediators (SPMs) decrease NF-kB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-kB regulation by SPMs remain to be determined. In this study, after LPS challenge, the SPMs 15-epi-lipoxin A4 (15-epi-LXA4), 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-kB regulators A20 and single Ig IL-1R–related molecule (SIGIRR). Of interest, 15-epi-LXA4 induced A20 and SIGIRR in an lipoxin A4 receptor/ formyl peptide receptor 2 (ALX/FPR2) receptor–dependent manner in epithelial cells and in murine pneumonia. This SPM regulated NF-kB–induced cytokines to decrease pathogen-mediated inflammation. In addition to dampening lung inflammation, surprisingly, 15-epi-LXA4 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-kB activity and to establish mechanisms for NF-kB regulation by SPMs for pneumonia resolution.

LanguageEnglish (US)
Pages2757-2766
Number of pages10
JournalJournal of Immunology
Volume200
Issue number8
DOIs
StatePublished - Apr 15 2018

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Bacterial Pneumonia
NF-kappa B
Pneumonia
Lipoxin Receptors
Epithelial Cells
Formyl Peptide Receptor
Inflammation
lipoxin A4
resolvin D2
resolvin D3
Cytokines
Lung
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Sham, H. P., Walker, K. H., Abdulnour, R. E. E., Krishnamoorthy, N., Douda, D. N., Norris, P. C., ... Levy, B. D. (2018). 15-epi-lipoxin A4, resolvin D2, and resolvin D3 induce NF-kB regulators in bacterial pneumonia. Journal of Immunology, 200(8), 2757-2766. https://doi.org/10.4049/jimmunol.1602090

15-epi-lipoxin A4, resolvin D2, and resolvin D3 induce NF-kB regulators in bacterial pneumonia. / 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 Long; Serhan, Charles N.; Levy, Bruce D.

In: Journal of Immunology, Vol. 200, No. 8, 15.04.2018, p. 2757-2766.

Research output: Contribution to journalArticle

Sham, HP, Walker, KH, Abdulnour, REE, Krishnamoorthy, N, Douda, DN, Norris, PC, Barkas, I, Benito-Figueroa, S, Colby, JKL, Serhan, CN & Levy, BD 2018, '15-epi-lipoxin A4, resolvin D2, and resolvin D3 induce NF-kB regulators in bacterial pneumonia' Journal of Immunology, vol. 200, no. 8, pp. 2757-2766. https://doi.org/10.4049/jimmunol.1602090
Sham HP, Walker KH, Abdulnour REE, Krishnamoorthy N, Douda DN, Norris PC et al. 15-epi-lipoxin A4, resolvin D2, and resolvin D3 induce NF-kB regulators in bacterial pneumonia. Journal of Immunology. 2018 Apr 15;200(8):2757-2766. https://doi.org/10.4049/jimmunol.1602090
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 Long ; Serhan, Charles N. ; Levy, Bruce D. / 15-epi-lipoxin A4, resolvin D2, and resolvin D3 induce NF-kB regulators in bacterial pneumonia. In: Journal of Immunology. 2018 ; Vol. 200, No. 8. pp. 2757-2766.
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