Aging Delays Resolution of Acute Inflammation in Mice: Reprogramming the Host Response with Novel Nano-Proresolving Medicines

Arnardottir, Hildur; Dalli, Jesmond; Colas, Romain A.; Shinohara, Masakazu; Serhan, Charles N.

doi:10.4049/jimmunol.1401313

Cited by 140 publications

(133 citation statements)

References 33 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…In response to oral omega-3 supplementation, our data display a decrease in the number of monocytes present in the mouse peritoneum following thioglycollate-induced chemical peritonitis, with no change in neutrophil or lymphocyte number. This stands in contrast to the results of prior chemical peritonitis studies in mice that have used intraperitoneal or intravenous administration of pro-resolution DHA and DHA-or EPAderived lipid mediator products, where moderate reductions in neutrophil influx 39 as well as alterations in efferocytotic capacity[40][41][42][43][44][45] were noted. We also observed an increase in the ratio of macrophages/ (monocytes + macrophages) in the peritoneal space in mice supplemented with fish oil, with no change in the number of macrophages present.…”

contrasting

confidence: 84%

Oral omega-3 fatty acids promote resolution in chemical peritonitis

Chacon

Phillips

Chacon

et al. 2016

Journal of Surgical Research

View full text Add to dashboard Cite

contrasting

confidence: 84%

Oral omega-3 fatty acids promote resolution in chemical peritonitis

Chacon

Phillips

Chacon

et al. 2016

Journal of Surgical Research

View full text Add to dashboard Cite

“…30,31 Of interest, intervention with nanoparticles designed to deliver AT-RvD3 and AT-RvD1 is able to rescue age-related delays in the normal resolution process. 32 For the work presented herein, we elected to focus on the 17R (AT) epimer of RvD3 for in vivo experiments on the basis of its longer half-life and favorable pharmacological properties relative to RvD3. 12,20 Lung edema is considered a defining characteristic of ALI/ARDS and understanding how to control its development and progression, as well as promote its resolution, remains an important clinical challenge.…”

Section: Discussionmentioning

confidence: 99%

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Colby

Abdulnour

Sham

et al. 2016

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acidederived mediator resolvin D3 (RvD3): 4S,11R,17S-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acideinitiated injury. Because of its delayed enzymatic degradation, we used aspirin-triggered (AT)-RvD3: 4S,11R,17R-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid, a 17R-epimer of RvD3, for in vivo experiments. Histopathological correlates of acid injury (alveolar wall thickening, edema, and leukocyte infiltration) were reduced in mice receiving AT-RvD3 1 hour after injury. AT-RvD3etreated mice had significantly reduced edema, as demonstrated by lower wet/dry weight ratios, increased epithelial sodium channel g expression, and more lymphatic vessel endothelial hyaluronan receptor 1-positive vascular endothelial growth factor receptor 3-positive lymphatic vessels. Evidence for counterregulation of NF-kB by RvD3 and AT-RvD3 was seen in vitro and by AT-RvD3 in vivo. Increases in lung epithelial cell proliferation and bronchoalveolar lavage fluid levels of keratinocyte growth factor were observed with AT-RvD3, which also promoted cutaneous re-epithelialization. Together, these data demonstrate protective actions of RvD3 and AT-RvD3 for injured mucosa that accelerated restoration of epithelial barrier and function. (Am J Pathol 2016 http://dx.doi.org/10.1016/j.ajpath.2016 Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious conditions characterized by loss of normal epithelial and endothelial barrier function, leading to pulmonary edema and infiltration of leukocytes culminating in significant impairments in gas exchange. 1 ARDS and its milder form, ALI, are serious conditions characterized by loss of normal epithelial and endothelial barrier function, leading to pulmonary edema and infiltration of leukocytes culminating in significant impairments in gas exchange. 1 ALI is a common condition, affecting approximately 200,000 patients a year in the United States alone. 2 Although our understanding of the pathophysiological changes associated with ALI/ARDS has improved since its original description, effective management of this condition still proves difficult, and mortality remains approximately 40%. 2 Aspiration pneumonia/pneumonitis is a common cause of ALI/ARDS characterized by direct damage to lung epithelia (because of the low pH of gastric contents) followed by extensive sloughing of the injured epithelial cells. 3 Despite significant damage to the epithelial barrier,

show abstract

“…114 Recent evidence indicates that aging mice display a dysregulated resolution response to acute inflammation, and the SPM RvD3 has beneficial effects in this scenario. 115,116 Thus, SPMs have potential as next generation therapeutics for promoting resolution of inflammation and reparative responses without the immunosuppressive effects observed with current anti-inflammatory drugs. 112,114 SPMs indeed increase survival from bacterial and viral infections in mice.…”

Section: Mediators Of Resolution Of Inflammation and Wound Healingmentioning

confidence: 99%

Wound repair: role of immune–epithelial interactions

Leoni¹,

Neumann²,

et al. 2015

View full text Add to dashboard Cite

The epithelium serves as a highly selective barrier at mucosal surfaces. Upon injury, epithelial wound closure is orchestrated by a series of events that emanate from the epithelium itself as well as by the temporal recruitment of immune cells into the wound bed. Epithelial cells adjoining the wound flatten out, migrate, and proliferate to rapidly cover denuded surfaces and re-establish mucosal homeostasis. This process is highly regulated by proteins and lipids, proresolving mediators such as Annexin A1 protein and resolvins released into the epithelial milieu by the epithelium itself and infiltrating innate immune cells including neutrophils and macrophages. Failure to achieve these finely tuned processes is observed in chronic inflammatory diseases that are associated with non-healing wounds. An improved understanding of mechanisms that mediate repair is important in the development of therapeutics aimed to promote mucosal wound repair.

show abstract

Aging Delays Resolution of Acute Inflammation in Mice: Reprogramming the Host Response with Novel Nano-Proresolving Medicines

Cited by 140 publications

References 33 publications

Oral omega-3 fatty acids promote resolution in chemical peritonitis

Oral omega-3 fatty acids promote resolution in chemical peritonitis

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Wound repair: role of immune–epithelial interactions

Contact Info

Product

Resources

About