TY - JOUR
T1 - 15-epi-lipoxin A 4 , resolvin D2, and resolvin D3 induce NF-kB regulators in bacterial pneumonia
AU - Sham, Ho Pan
AU - Walker, Katherine H.
AU - Abdulnour, Raja Elie E.
AU - Krishnamoorthy, Nandini
AU - Douda, David N.
AU - Norris, Paul C.
AU - Barkas, Ioanna
AU - Benito-Figueroa, Sarah
AU - Colby, Jennifer K.
AU - Serhan, Charles N.
AU - Levy, Bruce D.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants P01-GM095467 (to B.D.L. and C.N.S.), K08-HL130540 (to R.-E.E.A.), 2T32HL007633-31 (to B.D.L. and K.H.W.), and F32 AI134019-01 (to K.H.W.), as well as a Canadian Institute of Health Research postdoctoral fellowship (to H.P.S. and D.N.D.).
Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018/4/15
Y1 - 2018/4/15
N2 - 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 A 4 (15-epi-LXA 4 ), 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-LXA 4 induced A20 and SIGIRR in an lipoxin A 4 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-LXA 4 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.
AB - 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 A 4 (15-epi-LXA 4 ), 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-LXA 4 induced A20 and SIGIRR in an lipoxin A 4 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-LXA 4 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.
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U2 - 10.4049/jimmunol.1602090
DO - 10.4049/jimmunol.1602090
M3 - Article
C2 - 29523657
AN - SCOPUS:85045638587
SN - 0022-1767
VL - 200
SP - 2757
EP - 2766
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -