Resolvin D1 and D2 reduce SARS‐CoV‐2‐induced inflammatory responses in cystic fibrosis macrophages

AbstractResolvins (Rv) are endogenous lipid autacoids that mediate resolution of inflammation and bacterial infections. Their roles in SARS-CoV-2 and COVID-19 are of considerable interest in the context of cystic fibrosis (CF) given the paucity of data regarding the effect of this virus on immune cells from individuals with CF. Here, we provide evidence for Rv biosynthesis and regulatory actions on CF macrophage inflammatory responses.

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Resolvin D1 regulates epithelial ion transport and inflammation in cystic fibrosis airways

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2017.11.017 ◽

2018 ◽

Vol 17 (5) ◽

pp. 607-615 ◽

Cited By ~ 14

Author(s):

Fiona C. Ringholz ◽

Gerard Higgins ◽

Aurélie Hatton ◽

Ali Sassi ◽

Ahmad Moukachar ◽

...

Keyword(s):

Cystic Fibrosis ◽

Ion Transport ◽

Resolvin D1 ◽

Epithelial Ion Transport

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The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review

International Journal of Molecular Sciences ◽

10.3390/ijms22094370 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4370

Author(s):

Cássia de Fáveri ◽

Paula M. Poeta Fermino ◽

Anna P. Piovezan ◽

Lia K. Volpato

Keyword(s):

Intracellular Signaling ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Critical Role ◽

Integrative Review ◽

Inflammatory Factors ◽

Resolvin D1 ◽

Endogenous Factors

The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions’ progression, attenuating pro-inflammatory and angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors. Annexin A1 is expressed in the endometrium and is specifically present in women with endometriosis, although the available studies are still inconsistent. Thus, we believe there is a gap in knowledge regarding the PRM pathways in patients with endometriosis. It is important to note that these substances’ therapeutic potential is evident since the immune and abnormal inflammatory responses play an essential role in endometriosis development and progression.

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Nutritional Effects on Host Response to Lung Infections with Mucoid Pseudomonas aeruginosa in Mice

Infection and Immunity ◽

10.1128/iai.72.3.1479-1486.2004 ◽

2004 ◽

Vol 72 (3) ◽

pp. 1479-1486 ◽

Cited By ~ 15

Author(s):

Anna M. van Heeckeren ◽

Mark Schluchter ◽

Lintong Xue ◽

Juan Alvarez ◽

Steven Freedman ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Docosahexaenoic Acid ◽

Knockout Mice ◽

Host Response ◽

Inflammatory Responses ◽

Liquid Diet ◽

Wild Type ◽

Agarose Beads ◽

Lung Infections

ABSTRACT In cystic fibrosis, a recessive genetic disease caused by defects in the cystic fibrosis conductance regulator (CFTR), the main cause of death is lung infection and inflammation. Nutritional deficits have been proposed to contribute to the excessive host inflammatory response in both humans and Cftr-knockout mice. Cftr-knockout mice and gut-corrected Cftr-knockout mice expressing human CFTR primarily in the gut were challenged with Pseudomonas aeruginosa-laden agarose beads; they responded similarly with respect to bronchoalveolar lavage cell counts and levels of the acute-phase cytokines tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-6. Wild-type mice fed the liquid diet used to prevent intestinal obstruction in Cftr-knockout mice had inflammatory responses to P. aeruginosa-laden agarose beads similar to those of wild-type mice fed an enriched solid diet, so dietary effects are unlikely to account for differences between wild-type mice and mice with cystic fibrosis. Finally, since cystic fibrosis patients and Cftr-knockout mice have an imbalance in fatty acids (significantly lower-than-normal levels of docosahexaenoic acid), the effects of specific supplementation with docosahexaenoic acid of wild-type and Cftr-knockout mice on their inflammatory responses to P. aeruginosa-laden agarose beads were tested. There were no significant differences (P = 0.35) in cumulative survival rates between Cftr-knockout mice and wild-type mice provided with either the liquid diet Peptamen or Peptamen containing docosahexaenoic acid. In conclusion, diet and docosahexaenoic acid imbalances alone are unlikely to explain the differences in the host response to lung infections with mucoid P. aeruginosa between mice with cystic fibrosis and their wild-type counterparts.

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Development of IgG antibodies to Exophiala dermatitidis is associated with inflammatory responses in patients with cystic fibrosis

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2013.12.007 ◽

2014 ◽

Vol 13 (4) ◽

pp. 391-399 ◽

Cited By ~ 27

Author(s):

Nahid Kondori ◽

Anders Lindblad ◽

Christina Welinder-Olsson ◽

Christine Wennerås ◽

Marita Gilljam

Keyword(s):

Cystic Fibrosis ◽

Inflammatory Responses ◽

Igg Antibodies ◽

Exophiala Dermatitidis

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Resolvin D1 Administration Is Beneficial in Trypanosoma cruzi Infection

Infection and Immunity ◽

10.1128/iai.00052-20 ◽

2020 ◽

Vol 88 (6) ◽

Cited By ~ 1

Author(s):

Aline L. Horta ◽

Tere Williams ◽

Bing Han ◽

Yanfen Ma ◽

Ana Paula J. Menezes ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Chronic Infection ◽

Transforming Growth Factor ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Acute Infection ◽

Public Health Issue ◽

Resolvin D1 ◽

Content Type

ABSTRACT Chagas disease is a major public health issue, affecting ∼10 million people worldwide. Transmitted by a protozoan named Trypanosoma cruzi, this infection triggers a chronic inflammatory process that can lead to cardiomyopathy (Chagas disease). Resolvin D1 (RvD1) is a novel proresolution lipid mediator whose effects on inflammatory diseases dampens pathological inflammatory responses and can restore tissue homeostasis. Current therapies are not effective in altering the outcome of T. cruzi infection, and as RvD1 has been evaluated as a therapeutic agent in various inflammatory diseases, we examined if exogenous RvD1 could modulate the pathogenesis of Chagas disease in a murine model. CD-1 mice infected with the T. cruzi Brazil strain were treated with RvD1. Mice were administered 3 μg/kg of body weight RvD1 intraperitoneally on days 5, 10, and 15 to examine the effect of RvD1 on acute disease or administered the same dose on days 60, 65, and 70 to examine its effects on chronic infection. RvD1 therapy increased the survival rate and controlled parasite replication in mice with acute infection and reduced the levels of interferon gamma and transforming growth factor β (TGF-β) in mice with chronic infection. In addition, there was an increase in interleukin-10 levels with RvD1 therapy in both mice with acute infection and mice with chronic infection and a decrease in TGF-β levels and collagen content in cardiac tissue. Together, these data indicate that RvD1 therapy can dampen the inflammatory response, promote the resolution of T. cruzi infection, and prevent cardiac fibrosis.

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Alleviation of depression-like behavior in a cystic fibrosis mouse model by Hdac6 depletion

Scientific Reports ◽

10.1038/s41598-020-73298-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Deborah A. Corey ◽

Sharon M. Rymut ◽

Thomas J. Kelley

Keyword(s):

Cystic Fibrosis ◽

Growth Regulation ◽

Inflammatory Responses ◽

Tail Suspension Test ◽

Dependent Manner ◽

Treatment Regimens ◽

Elevated Plus Maze Test ◽

Rigorous Treatment ◽

Inflammatory Phenotypes ◽

Patients Experience

Abstract Cystic fibrosis (CF) patients experience heightened levels of anxiety and depression. Stress from dealing with chronic disease and rigorous treatment regimens certainly are primary contributors to these outcomes. We previously have demonstrated that microtubule alterations in CF are linked to a number of CF phenotypes including growth regulation and inflammatory responses to airway bacterial challenge. Deletion of histone deactelyase 6 (HDAC6), a cytosolic deacetylase that regulates tubulin acetylation, in CF mice restores growth and inflammatory phenotypes to wild type (WT) profiles. In this study, the hypothesis that Hdac6 depletion in CF mice would impact behaviors since Hda6 inhibition has been previously reported to have anti-depressive properties. Data demonstrate that CF mice exhibit reduced activity and reduced open arm time in an elevated plus maze test which can be consistent with anxiety-like behavior. CF mice also exhibit depression-like behaviors compared to WT mice in an age dependent manner. By eight weeks of age, CF mice exhibit significantly more immobile time in the tail-suspension test, however, Hdac6 depletion reverses the depressive phenotype. These data demonstrate that loss of CFTR function may predispose patients to experience depression and that this behavior is Hdac6 dependent.

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