Limits...
Vagus nerve controls resolution and pro-resolving mediators of inflammation.

Mirakaj V, Dalli J, Granja T, Rosenberger P, Serhan CN - J. Exp. Med. (2014)

Bottom Line: In netrin-1(+/-) mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1(+/+).Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins.Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other's expression and enhanced efferocytosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 Clinic of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard-Karls University, 72076 Tübingen, Germany.

Show MeSH

Related in: MedlinePlus

RvD1 rescues hyperinflammation in vagotomized mice. Vagotomized or sham-operated control mice were injected i.p. with zymosan A (ZyA) and subsequently with RvD1 (RvD1). Peritoneal lavages were collected at indicated time points. (A) Total leukocytes were enumerated by light microscopy. PMN, classical monocytes, and nonclassical monocytes were determined by flow cytometry. (B) TNF, IL-6, KC, MIP-1α, and HMGB1 were measured in exudates by ELISA. Results are mean ± SEM, n = 6 per group for two independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4042652&req=5

fig3: RvD1 rescues hyperinflammation in vagotomized mice. Vagotomized or sham-operated control mice were injected i.p. with zymosan A (ZyA) and subsequently with RvD1 (RvD1). Peritoneal lavages were collected at indicated time points. (A) Total leukocytes were enumerated by light microscopy. PMN, classical monocytes, and nonclassical monocytes were determined by flow cytometry. (B) TNF, IL-6, KC, MIP-1α, and HMGB1 were measured in exudates by ELISA. Results are mean ± SEM, n = 6 per group for two independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Mentions: Because vagotomy reduced RvD1 levels, we tested whether RvD1 could rescue the hyperinflammatory response obtained with vagotomy. Indeed, results in Fig. 3 indicate that administration of RvD1 rescued the excessive increased PMN infiltration that resulted from vagotomy (caused by vagus nerve cutting). RvD1 stopped PMN influx in the vagotomized animals and regulated the exudate monocyte recruitment (Fig. 3 A). In these exudates, RvD1 also reduced TNF, IL-6, KC (IL-8 in humans), MIP-1α, and HMGB-1 (Fig. 3 B). Also, netrin-1 reduced Ri when given at either T0 (Fig. 4 A) or at the maximum PMN infiltration (Fig. 4 B). In both cases, netrin-1 shortened the time required to resolve inflammation.


Vagus nerve controls resolution and pro-resolving mediators of inflammation.

Mirakaj V, Dalli J, Granja T, Rosenberger P, Serhan CN - J. Exp. Med. (2014)

RvD1 rescues hyperinflammation in vagotomized mice. Vagotomized or sham-operated control mice were injected i.p. with zymosan A (ZyA) and subsequently with RvD1 (RvD1). Peritoneal lavages were collected at indicated time points. (A) Total leukocytes were enumerated by light microscopy. PMN, classical monocytes, and nonclassical monocytes were determined by flow cytometry. (B) TNF, IL-6, KC, MIP-1α, and HMGB1 were measured in exudates by ELISA. Results are mean ± SEM, n = 6 per group for two independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4042652&req=5

fig3: RvD1 rescues hyperinflammation in vagotomized mice. Vagotomized or sham-operated control mice were injected i.p. with zymosan A (ZyA) and subsequently with RvD1 (RvD1). Peritoneal lavages were collected at indicated time points. (A) Total leukocytes were enumerated by light microscopy. PMN, classical monocytes, and nonclassical monocytes were determined by flow cytometry. (B) TNF, IL-6, KC, MIP-1α, and HMGB1 were measured in exudates by ELISA. Results are mean ± SEM, n = 6 per group for two independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Mentions: Because vagotomy reduced RvD1 levels, we tested whether RvD1 could rescue the hyperinflammatory response obtained with vagotomy. Indeed, results in Fig. 3 indicate that administration of RvD1 rescued the excessive increased PMN infiltration that resulted from vagotomy (caused by vagus nerve cutting). RvD1 stopped PMN influx in the vagotomized animals and regulated the exudate monocyte recruitment (Fig. 3 A). In these exudates, RvD1 also reduced TNF, IL-6, KC (IL-8 in humans), MIP-1α, and HMGB-1 (Fig. 3 B). Also, netrin-1 reduced Ri when given at either T0 (Fig. 4 A) or at the maximum PMN infiltration (Fig. 4 B). In both cases, netrin-1 shortened the time required to resolve inflammation.

Bottom Line: In netrin-1(+/-) mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1(+/+).Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins.Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other's expression and enhanced efferocytosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 Clinic of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard-Karls University, 72076 Tübingen, Germany.

Show MeSH
Related in: MedlinePlus