Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury

Eickmeier, Olaf; Seki, Hiroyuki; Haworth, Oliver; Hilberath, Jan N.; Gao, Fangfei; Uddin, Mohib; Croze, Roxanne H.; Carlo, Troy; Pfeffer, Michael; Levy, Bruce D.

doi:10.1038/mi.2012.66

Cited by 164 publications

(178 citation statements)

References 47 publications

Supporting

Mentioning

171

Contrasting

Order By: Relevance

“…Herein, AT-RvD3 regulation of NF-kB serves as a protective mechanism to modulate the immune response to acid injury. 8,25 Restoration of a fully functioning epithelial barrier is critical for complete resolution of mucosal tissue injury. 47 Impaired healing in general is a major clinical issue, and there is still a need to further our understanding of normal repair mechanisms to develop better approaches to promote successful tissue regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…8 Tissues were embedded, divided into sections, and stained with hematoxylin and eosin by either the Dana Farber/Harvard Cancer Center Rodent Histopathology Core or the Brigham and Women's Pulmonary and Critical Care Medicine Histology Core. Tissue sections were deparaffinized and rehydrated in graded ethanols and water; a subset of slides was stained with hematoxylin and eosin following standard protocols.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…7 Members of this series, including resolvin D1 (RvD1) and RvD2, have been shown to possess potent proresolving properties in models of acute inflammation, including the lung. 8e10 Earlier work from our group demonstrated host-protective functions of aspirin-triggered (AT)-RvD1 in murine models of ARDS 8 and allergic airway inflammation. 11 Recently, the biosynthetic routes and complete stereochemistry for resolvin D3 (RvD3) and its aspirin-triggered epimer AT-RvD3 were elucidated.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

Colby

Abdulnour

Sham

et al. 2016

The American Journal of Pathology

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

Section: Discussionmentioning

confidence: 99%

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

Colby

Abdulnour

Sham

et al. 2016

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…17,18 RvD1, which possesses anti-inflammatory and pro-resolving ability in many process of inflammatory resolution, has demonstrated that it can attenuate inflammatory responses in ALI, 10,11 peritonitis, 19,20 kidney ischemia-reperfusion injury, 21 and retinopathy. 22 Here our study was focused on the effects of RvD1 on disruption of pulmonary barrier in ALI and was undertaken to investigate possible molecular and cellular mechanism of RvD1.…”

Section: Discussionmentioning

confidence: 99%

“…8 Previous studies have showed that RvD1 displays potent anti-oxidative stress, 9 anti-inflammation, and pro-resolving actions that have been demonstrated in mouse models of ALI. [10][11][12] Though they have been observed that RvD1 can reduce pulmonary edema induced by lipopolysaccharide (LPS), the effects of RvD1 on TJ protein remain elusive.…”

mentioning

confidence: 99%

Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1 in LPS-induced mice

Xie

Wang

et al. 2013

Laboratory Investigation

View full text Add to dashboard Cite

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary permeability with high mortality. Resolvin D1 (RvD1), which has potent anti-inflammatory and pro-resolving activity, can attenuate pulmonary edema in the animal model of ALI. However, the mechanism underlying the protection of RvD1 on pulmonary edema is still unknown. Here we explore the effects and mechanism of RvD1 on the disruption of tight junction protein that results in the permeability edema in a model of lipopolysaccharide (LPS)-induced ALI. The severity of pulmonary edema was assessed by wet-to-dry rate and Evans blue infiltration; expressions of tight junction (TJ) proteins occludin and zona occludin-1 (ZO-1) were examined by immunofluorescence staining and western blot; mRNA in lung tissue was studied by real time-PCR; the TUNEL kit was performed for the detection of apoptosis of pulmonary barrier. Twenty-four hours after LPS inhalation by mice, wet-to-dry rate and Evans blue infiltration indicated that pretreatment with RvD1 relieved the pulmonary edema and pulmonary capillary permeability. Moreover, RvD1 attenuated the LPS-induced deterioration of TJ protein ZO-1 and occludin significantly. And we found that RvD1 increased heme oxygenase-1 (HO-1) expression contributed to the protection on the deterioration of TJs. In addition, we found that RvD1 could reduce pulmonary cellular apoptosis in LPS-induced mice. In conclusion, RvD1 possesses the ability that relieves the pulmonary edema and restores pulmonary capillary permeability and reduces disruption of TJs in LPS-induced ALI of mice, at least in part, by upregulating HO-1 expression.

show abstract

Roles of resolvins in the resolution of acute inflammation

Xuan

Fan

2014

Cell Biology International

View full text Add to dashboard Cite

Resolution is an active process that terminates inflammatory response to maintain health. Acute inflammation and its timely resolution are important in host response to danger signals. Unresolved inflammation is associated with widely recurrent diseases. Resolvins, including the D and E series, are endogenous lipid mediators generated during the resolution phase of acute of inflammation from the ω-3 PUFAs, DHA, and EPA. They have anti-inflammatory and pro-resolving properties that have been determined in many inflammation studies in animal models. In this review, we provide an updated overview of biosynthesis, actions, and signaling pathways of resolvins, thereby underscoring their diverse protective roles and introducing novel therapeutic strategies for inflammation-associated diseases.

show abstract

Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury

Cited by 164 publications

References 47 publications

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

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

Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1 in LPS-induced mice

Roles of resolvins in the resolution of acute inflammation

Contact Info

Product

Resources

About