The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution

Serhan, Charles N.; Chiang, Nan; Dalli, Jesmond

doi:10.1016/j.smim.2015.03.004

Cited by 479 publications

(442 citation statements)

References 199 publications

(245 reference statements)

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“…Two decades of research now support the concept that resolution of inflammation is an active process brought about by specific mediators and receptors (12). We studied herein resolution, or its lack, in the persistent and unresolved inflammation typical of IBD (1).…”

Section: Discussionmentioning

confidence: 95%

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Protectin D1 _{n-3 DPA} and resolvin D5 _{n-3 DPA} are effectors of intestinal protection

Gobbetti

Dalli

Colas

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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143

105

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The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPM) that limit the host response within the affected tissue; failure of effective resolution may lead to tissue injury. Because persistence of inflammatory signals is a main feature of chronic inflammatory conditions, including inflammatory bowel diseases (IBDs), herein we investigate expression and functions of SPM in intestinal inflammation. Targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was used to identify SPMs from n-3 polyunsaturated fatty acids in human IBD colon biopsies, quantifying a significant upregulation of the resolvin and protectin pathway compared with normal gut tissue. Systemic treatment with protectin (PD)1 n-3 DPA or resolvin (Rv)D5 n-3 DPA protected against colitis and intestinal ischemia/reperfusion-induced inflammation in mice. Inhibition of 15-lipoxygenase activity reduced PD1 n-3 DPA and augmented intestinal inflammation in experimental colitis. Intravital microscopy of mouse mesenteric venules demonstrated that PD1 n-3 DPA and RvD5 n-3 DPA decreased the extent of leukocyte adhesion and emigration following ischemia-reperfusion. These data were translated by assessing human neutrophil-endothelial interactions under flow: PD1 n-3 DPA and RvD5 n-3 DPA reduced cell adhesion onto TNF-α-activated human endothelial monolayers. In conclusion, we propose that innovative therapies based on n-3 DPA-derived mediators could be developed to enable antiinflammatory and tissue protective effects in inflammatory pathologies of the gut.inflammation resolution | specialized proresolving mediators | omega-3 fatty acids | intravital microscopy | neutrophils

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Section: Discussionmentioning

confidence: 95%

“…We propose that n-3 DPA-derived mediators could represent the basis for innovative therapeutic strategies in settings of intestinal inflammation. dampen inflammatory pain, and promote tissue repair and regeneration (12).…”

Section: Significancementioning

confidence: 99%

Protectin D1 _{n-3 DPA} and resolvin D5 _{n-3 DPA} are effectors of intestinal protection

Gobbetti

Dalli

Colas

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

143

105

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“…This is consistent with studies demonstrating positive feedback between early neutrophil influx and recruitment of inflammatory monocytes, which can be mediated by a variety of neutrophil products. 45 Although other factors contributing to delayed resolution of inflammation in NADPH oxidase deficiency remain to be investigated, such as proresolving lipid mediators, 46 the current findings establish a link between prolonged inflammation and the amplified acute neutrophil recruitment to injured tissue via an upregulated IL-1a/G-CSF axis.…”

Section: Org Frommentioning

confidence: 67%

NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating the IL-1α/G-CSF axis

Bagaitkar¹,

Pech²,

Ivanov

et al. 2015

Blood

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“…Moreover, PGE 2 and PGD 2, as well as the acetylation of COX-2 triggered by aspirin, actively mobilized the biosynthesis of other proresolving lipid mediators, such as lipoxins and resolvins, to dominate the resolution phase (14,29,40). Therefore, COX-2 may play a causative role in the switch from inflammation initiation to resolution (41).…”

Section: Discussionmentioning

confidence: 99%

Resolvin D1 Improves the Resolution of Inflammation via Activating NF-κB p50/p50–Mediated Cyclooxygenase-2 Expression in Acute Respiratory Distress Syndrome

Gao

Zhang

Luo

et al. 2017

The Journal of Immunology

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Acute respiratory distress syndrome (ARDS) is a severe illness characterized by uncontrolled inflammation. The resolution of inflammation is a tightly regulated event controlled by endogenous mediators, such as resolvin D1 (RvD1). Cyclooxygenase-2 (COX-2) has been reported to promote inflammation, along with PGE2, in the initiation of inflammation, as well as in prompting resolution, with PGD2 acting in the later phase of inflammation. Our previous work demonstrated that RvD1 enhanced COX-2 and PGD2 expression to resolve inflammation. In this study, we investigated mechanisms underlying the effect of RvD1 in modulating proresolving COX-2 expression. In a self-limited ARDS model, an LPS challenge induced the biphasic activation of COX-2, and RvD1 promoted COX-2 expression during the resolution phase. However, it was significantly blocked by treatment of a NF-κB inhibitor. In pulmonary fibroblasts, NF-κB p50/p50 was shown to be responsible for the proresolving activity of COX-2. Additionally, RvD1 potently promoted p50 homodimer nuclear translocation and robustly triggered DNA-binding activity, upregulating COX-2 expression via lipoxin A4 receptor/formyl peptide receptor 2. Finally, the absence of p50 in knockout mice prevented RvD1 from promoting COX-2 and PGD2 expression and resulted in excessive pulmonary inflammation. In conclusion, RvD1 expedites the resolution of inflammation through activation of lipoxin A4 receptor/formyl peptide receptor 2 receptor and NF-κB p50/p50–COX-2 signaling pathways, indicating that RvD1 might have therapeutic potential in the management of ARDS.

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The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution

Cited by 479 publications

References 199 publications

Protectin D1 _{n-3 DPA} and resolvin D5 _{n-3 DPA} are effectors of intestinal protection

Protectin D1 _{n-3 DPA} and resolvin D5 _{n-3 DPA} are effectors of intestinal protection

NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating the IL-1α/G-CSF axis

Resolvin D1 Improves the Resolution of Inflammation via Activating NF-κB p50/p50–Mediated Cyclooxygenase-2 Expression in Acute Respiratory Distress Syndrome

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The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution

Cited by 479 publications

References 199 publications

Protectin D1 n-3 DPA and resolvin D5 n-3 DPA are effectors of intestinal protection

Protectin D1 n-3 DPA and resolvin D5 n-3 DPA are effectors of intestinal protection

NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating the IL-1α/G-CSF axis

Resolvin D1 Improves the Resolution of Inflammation via Activating NF-κB p50/p50–Mediated Cyclooxygenase-2 Expression in Acute Respiratory Distress Syndrome

Contact Info

Product

Resources

About

Protectin D1 _{n-3 DPA} and resolvin D5 _{n-3 DPA} are effectors of intestinal protection

Protectin D1 _{n-3 DPA} and resolvin D5 _{n-3 DPA} are effectors of intestinal protection