The Anti-Inflammatory and Proresolving Mediator Resolvin E1 Protects Mice from Bacterial Pneumonia and Acute Lung Injury

Seki, Hiroyuki; Fukunaga, Koichi; Arita, Makoto; Arai, Hiroyuki; Nakanishi, Hiroki; Taguchi, Ryo; Miyasho, Taku; Takamiya, Rina; Asano, Koichiro; Ishizaka, Akitoshi; Takeda, Junzo; Levy, Bruce D.

doi:10.4049/jimmunol.0901809

Cited by 196 publications

(199 citation statements)

References 56 publications

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“…49 RvD1 also directly inhibits neutrophil chemotaxis. 21,50 Here, we found that AT-RvD1 dramatically altered the inflammatory environment in cigarette smokeeexposed lungs, with reductions in total inflammatory cells, neutrophils, and the expression of proinflammatory cytokines, Cox-2, and ICAM-1, and increased expression of IL-10. We hypothesize that the reduction in inflammation results from both the direct inhibition of neutrophil chemotaxis and activation as well as inhibition of proinflammatory signaling by epithelial and other lung cells, resulting in decreased levels of expression of chemotactic factors and adhesion molecules.…”

Section: Discussionmentioning

confidence: 61%

“…We and others have reported that RvD1 promotes alternative activation of macrophages (the M2 phenotype) 11,50 and that the M2 macrophages appear to mitigate inflammation and promote the resolution of inflammation in acute models and cell culture systems. 11,51 However, some evidence suggests that in chronic diseases, M2 macrophages may promote tissue remodeling and repair, leading to fibrosis.…”

Section: Discussionmentioning

confidence: 87%

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Resolvin D1 Reduces Emphysema and Chronic Inflammation

Hsiao

Thatcher

Colas

et al. 2015

The American Journal of Pathology

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Chronic obstructive pulmonary disease is characterized, in part, by chronic inflammation that persists even after smoking cessation, suggesting that a failure to resolve inflammation plays an important role in the pathogenesis of the disease. It is widely recognized that the resolution of inflammation is an active process, governed by specialized proresolving lipid mediators, including lipoxins, resolvins, maresins, and protectins. Here, we report that proresolving signaling and metabolic pathways are disrupted in lung tissue from patients with chronic obstructive pulmonary disease, suggesting that supplementation with proresolving lipid mediators might reduce the development of emphysema by controlling chronic inflammation. Groups of mice were exposed long-term to cigarette smoke and treated with the proresolving mediator resolvin D1. Resolvin D1 was associated with a reduced development of cigarette smokeeinduced emphysema and airspace enlargement, with concurrent reductions in inflammation, oxidative stress, and cell death. Interestingly, resolvin D1 did not promote the differentiation of M2 macrophages and did not promote tissue fibrosis. Taken together, our results suggest that cigarette smoking disrupts endogenous proresolving pathways and that supplementation with specialized proresolving lipid mediators is an important therapeutic strategy in chronic lung disease, especially if endogenous specialized proresolving lipid mediator signaling is impaired. (Am J Pathol 2015, 185: 3189e3201; http:// dx.doi.org/10.1016/j.ajpath.2015 Chronic obstructive pulmonary disease (COPD) is a major global health problem and a leading cause of death and disability. Tobacco smoking remains the major causative factor in the development of COPD; however, new evidence suggests that household air pollution from fuel used for indoor cooking and heating is also a significant cause.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 87%

Resolvin D1 Reduces Emphysema and Chronic Inflammation

Hsiao

Thatcher

Colas

et al. 2015

The American Journal of Pathology

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“…19 A total of 1 Â 10 6 colony-forming units of Escherichia coli were introduced to the left mainstem bronchus (total volume, 25 mL). Mice were given ATRvD3 (10 ng, i.v.)…”

Section: E Coli Pneumoniamentioning

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

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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,

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“…RvE1 diminui a expressão de CD18 em Neutrófilos e Monócitos e modifica a ação da Lselectina (que está relacionada aos eventos iniciais do recrutamento de Leucócitos), resultando na redução da migração de Neutrófilos para o local da inflamação. 2,[54][55][56][57] As resolvinas são produzidas em resposta a um estímulo, têm ação local e têm metabolização por vias enzimáticas que levam à sua inativação. As RvE1 podem ser convertidas a diferentes metabólitos (20-hidroxi-RvE1, 20-carboxi-RvE1, 19-hidroxi-ReV1, 18-oxo-RvE1 e 10, 11-diidro-RvE1) em Neutrófilos humanos que são biologicamente inativos se comparados às RvE1.…”

Section: Resolvinas E Protectinas Resolvinas E Protectinas Resolvinasunclassified

“…As RvE1 podem ser convertidas a diferentes metabólitos (20-hidroxi-RvE1, 20-carboxi-RvE1, 19-hidroxi-ReV1, 18-oxo-RvE1 e 10, 11-diidro-RvE1) em Neutrófilos humanos que são biologicamente inativos se comparados às RvE1. 2,48,[55][56][57] …”

Section: Resolvinas E Protectinas Resolvinas E Protectinas Resolvinasunclassified

Papel dos ácidos graxos ômega 3 na resolução dos processos inflamatórios

Barbalho

Bechara

Quesada³

et al. 2011

Medicina (Ribeirão Preto)

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Artigo recebido em 09/12/2010 Aprovado para publicação em 13/09/2011 P P P P Pa a a a apel dos ácidos g pel dos ácidos g pel dos ácidos g pel dos ácidos g pel dos ácidos gr r r r rax ax ax ax axos ôme os ôme os ôme os ôme os ômeg g g g ga 3 na a 3 na a 3 na a 3 na a 3 na r r r r resolução dos pr esolução dos pr esolução dos pr esolução dos pr esolução dos processos inf ocessos inf ocessos inf ocessos inf ocessos inflama lama lama lama lamatórios tórios tórios tórios tórios RESUMOA inflamação é uma resposta de defesa do organismo ao trauma ou a infecções por microorganismos. Na fase de término da inflamação e retorno à homeostase ocorrem mecanismos de regulação chamados de resolução onde há alternância de prostaglandinas pró-inflamatórias e leucotrienos a mediadores pró-resolução, produzidos a partir de ácidos graxos poliinsaturados ω3 (ácido eicosapentanóico e ácido docosapentanóico). A dieta interfere na composição de ácidos graxos das membranas celulares que serão metabolizados em compostos ativos chamados de resolvinas, protectinas e maresinas. Como as doenças inflamatórias têm papel importante na saúde pública o estudo destas substâncias e o delineamento de seus efeitos podem trazer novos horizontes no tratamento das doenças inflamató-rias, com redução de custos e minimização de efeitos colaterais. Palavras-Chave:Inflamação. Ácidos Graxos Ômega-3. Resolvinas. Protectinas. Introdução Introdução Introdução Introdução IntroduçãoO processo inflamatório é uma resposta de defesa ao trauma ou a infecções microbianas e é iniciada com a finalidade de extinguir o estímulo que a desencadeou ou para remover um dano tissular. Muitas doenças como mal de Alzheimer, Diabetes, doenças cardiovasculares, asma, artrite reumatóide, periodontite, câncer e outras são resultantes de processos inflamatórios inapropriados ou excessivos que as iniciam e as acompanham de forma crônica. 1,2 Em condições favoráveis a resposta inflamató-ria aguda é adequada de tal forma que controla os eventos danosos ao tecido, por exemplo, para eliminar microorganismos invasores e para preparar o local para os processos de recuperação. Se os danos teciduais são de proporções tais que as células podem recuperar suas funções normais, dá-se o nome ao processo de resolução. No entanto, muitas vezes a lesão persiste e os mecanismos de cicatrização não se completam. A conseqüência é que são estimuladas as defesas do sistema imunológico com ativação de macró-fagos, liberação de mediadores químicos, metabólitos reativos (radicais livres), moléculas de adesão, proteases e enzimas hidrolíticas, citocinas inflamatórias, como as interleucinas (IL) e fator de necrose tumoral α (TNFα) e fatores de crescimento. [3][4][5][6][7][8][9] No caminho de término da inflamação em direção da homeostase, ou seja, no processo de resolução, ocorrem mecanismos de regulação ativa onde há

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The Anti-Inflammatory and Proresolving Mediator Resolvin E1 Protects Mice from Bacterial Pneumonia and Acute Lung Injury

Cited by 196 publications

References 56 publications

Resolvin D1 Reduces Emphysema and Chronic Inflammation

Resolvin D1 Reduces Emphysema and Chronic Inflammation

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

Papel dos ácidos graxos ômega 3 na resolução dos processos inflamatórios

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