Molecular circuits of resolution: Formation and actions of resolvins and protectins

Gerard L. Bannenberg, Nan Chiang, Amiram Ariel, Makoto Arita, Eric Tjonahen, Katherine H. Gotlinger, Song Hong, Charles N. Serhan

Research output: Contribution to journalArticle

459 Citations (Scopus)

Abstract

The cellular events underlying the resolution of acute inflammation are not known in molecular terms. To identify anti-inflammatory and proresolving circuits, we investigated the temporal and differential changes in self-resolving murine exudates using mass spectrometry-based proteomics and lipidomics. Key resolution components were defined as resolution indices including Ψmax, the maximal neutrophil numbers that are present during the inflammatory response; Tmax, the time when Ψmax occurs; and the resolution interval (Ri) from Tmax to T50 when neutrophil numbers reach half Ψmax. The onset of resolution was at ∼12 h with proteomic analysis showing both haptoglobin and S100A9 levels were maximal and other exudate proteins were dynamically regulated. Eicosanoids and polyunsaturated fatty acids first appeared within 4 h. Interestingly, the docosahexaenoic acid-derived anti-inflammatory lipid mediator 10,17S-docosatriene was generated during the Ri. Administration of aspirin-triggered lipoxin A 4 analog, resolvin E1, or 10,17S-docosatriene each either activated and/or accelerated resolution. For example, aspirin-triggered lipoxin A 4 analog reduced Ψmax, resolvin E1 decreased both Ψmax and Tmax, whereas 10,17S-docosatriene reduced Ψmax, Tmax, and shortened Ri. Also, aspirin-triggered lipexin A4 analog markedly inhibited proinflammatory cytokines and chemokines at 4 h (20-50% inhibition), whereas resolvin E1 and 10,17S-docosatriene's inhibitory actions were maximal at 12 h (30-80% inhibition). Moreover, aspirin-triggered lipoxin A4 analog evoked release of the antiphlogistic cytokine TGF-β. These results characterize the first molecular resolution circuits and their major components activated by specific novel lipid mediators (i.e., resolvin E1 and 10,17S-docosatriene) to promote resolution.

Original languageEnglish
Pages (from-to)4345-4355
Number of pages11
JournalJournal of Immunology
Volume174
Issue number7
Publication statusPublished - 2005 Apr 1
Externally publishedYes

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CD59 Antigens
Aspirin
Lipoxins
Exudates and Transudates
Proteomics
Neutrophils
Anti-Inflammatory Agents
Cytokines
Lipids
Haptoglobins
Eicosanoids
Docosahexaenoic Acids
Unsaturated Fatty Acids
Chemokines
Mass Spectrometry
Inflammation
5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Bannenberg, G. L., Chiang, N., Ariel, A., Arita, M., Tjonahen, E., Gotlinger, K. H., ... Serhan, C. N. (2005). Molecular circuits of resolution: Formation and actions of resolvins and protectins. Journal of Immunology, 174(7), 4345-4355.

Molecular circuits of resolution : Formation and actions of resolvins and protectins. / Bannenberg, Gerard L.; Chiang, Nan; Ariel, Amiram; Arita, Makoto; Tjonahen, Eric; Gotlinger, Katherine H.; Hong, Song; Serhan, Charles N.

In: Journal of Immunology, Vol. 174, No. 7, 01.04.2005, p. 4345-4355.

Research output: Contribution to journalArticle

Bannenberg, GL, Chiang, N, Ariel, A, Arita, M, Tjonahen, E, Gotlinger, KH, Hong, S & Serhan, CN 2005, 'Molecular circuits of resolution: Formation and actions of resolvins and protectins', Journal of Immunology, vol. 174, no. 7, pp. 4345-4355.
Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH et al. Molecular circuits of resolution: Formation and actions of resolvins and protectins. Journal of Immunology. 2005 Apr 1;174(7):4345-4355.
Bannenberg, Gerard L. ; Chiang, Nan ; Ariel, Amiram ; Arita, Makoto ; Tjonahen, Eric ; Gotlinger, Katherine H. ; Hong, Song ; Serhan, Charles N. / Molecular circuits of resolution : Formation and actions of resolvins and protectins. In: Journal of Immunology. 2005 ; Vol. 174, No. 7. pp. 4345-4355.
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