The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
15-Epi-lipoxin A 4 Inhibits Myeloperoxidase Signaling and Enhances Resolution of Acute Lung Injury
Open accessAbstract
RATIONALE: Apoptosis is essential for removal of neutrophils from inflamed tissues and efficient resolution of inflammation. Myeloperoxidase (MPO), abundantly expressed in neutrophils, not only generates cytotoxic oxidants but also signals through the beta(2) integrin Mac-1 to rescue neutrophils from constitutive apoptosis, thereby prolonging inflammation. OBJECTIVES: Because aspirin-triggered 15-epi-lipoxin A(4) (15-epi-LXA(4)) modulates Mac-1 expression, we investigated the impact of 15-epi-LXA(4) on MPO suppression of neutrophil apoptosis and MPO-mediated neutrophil-dependent acute lung injury. METHODS: Human neutrophils were cultured with MPO with or without 15-epi-LXA(4) to investigate development of apoptosis. Acute lung injury was produced by intratracheal injection of carrageenan plus MPO or intraperitoneal injection of live Escherichia coli in mice, and the animals were treated with 15-epi-LXA(4) at the peak of inflammation. MEASUREMENTS AND MAIN RESULTS: 15-Epi-LXA(4) through down-regulation of Mac-1 expression promoted apoptosis of human neutrophils by attenuating MPO-induced activation of extracellular signal-regulated kinase and Akt-mediated phosphorylation of Bad and by reducing expression of the antiapoptotic protein Mcl-1, thereby aggravating mitochondrial dysfunction. The proapoptotic effect of 15-epi-LXA(4) was dominant over MPO-mediated effects even when it was added at 4 hours post MPO. In mice, treatment with 15-epi-LXA(4) accelerated the resolution of established carrageenan plus MPO-evoked as well as E. coli-induced neutrophil-dependent pulmonary inflammation through redirecting neutrophils to caspase-mediated cell death and facilitating their removal by macrophages. CONCLUSIONS: These results demonstrate that aspirin-triggered 15-epi-LXA(4) enhances resolution of inflammation by overriding the powerful antiapoptosis signal from MPO, thereby demonstrating a hitherto unrecognized mechanism by which aspirin promotes resolution of inflammation.
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Points of control in inflammation
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Resolution of in flammation: state of the art, definitions and terms
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“15-Epi-LXA4 is believed to promote recruitment of monocytes in a nonphlogistic fashion, consistent with facilitation of tissue repair (5, 22, 48).”
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Self-citationHypochlorous Acid Stimulation of the Mitogen-Activated Protein Kinase Pathway Enhances Cell Survival
Midwinter, R. G., Vissers, M. C. M., & Winterbourn, C. C. (2001) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2001.2530 · Cited by 90
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Resolvins and protectins in inflammation resolution
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Self-citationNarasaraju, T., Yang, E., Samy, R. P., Ng, H. H., Poh, W. P., Liew, A.-A., Phoon, M. C., van Rooijen, N., & Chow, V. T. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.03.013 · Cited by 890
Resolution of inflammation: an integrated view
Ortega‐Gómez, A., Perretti, M., & Soehnlein, O. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201202382 · Cited by 733
Infection regulates pro-resolving mediators that lower antibiotic requirements
Chiang, N., Fredman, G., Bäckhed, F., Oh, S. F., Vickery, T., Schmidt, B. A., & Serhan, C. N. (2012) · Nature · doi:10.1038/nature11042 · Cited by 664
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Metadata
- Authors
- El Kebir, D., József, L., Pan, W., Wang, L., Petasis, N. A., Serhan, C. N., & Filep, J. G.
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-08-15
- Volume
- 180
- Issue
- 4
- Pages
- 311-319
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2134294696
- Cited by
- 205
- References
- 5
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- green
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- El Kebir, D., József, L., Pan, W., Wang, L., Petasis, N. A., Serhan, C. N., & Filep, J. G. (2009). 15-Epi-lipoxin A 4 Inhibits Myeloperoxidase Signaling and Enhances Resolution of Acute Lung Injury. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.200810-1601oc
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