scholarly journals Resolvin D1 and D2 reduce SARS-Cov-2-induced inflammation in cystic fibrosis macrophages

2020 ◽  
Author(s):  
Antonio Recchiuti ◽  
Sara Patruno ◽  
Domenico Mattoscio ◽  
Elisa Isopi ◽  
Antonella Pomilio ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Immune Cells ◽  
Bacterial Infections ◽  
Inflammatory Responses ◽  
Resolvin D1 ◽  
Resolution Of Inflammation ◽  
Endogenous Lipid ◽  
Regulatory Actions

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.

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

2021 ◽  
Vol 35 (4) ◽  
Author(s):  
Antonio Recchiuti ◽  
Sara Patruno ◽  
Domenico Mattoscio ◽  
Elisa Isopi ◽  
Antonella Pomilio ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Inflammatory Responses ◽  
Resolvin D1

scholarly journals MiR-146a is over-expressed and controls IL-6 production in cystic fibrosis macrophages

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Francesco R. Luly ◽  
Manuella Lévêque ◽  
Valerio Licursi ◽  
Giuseppe Cimino ◽  
Corinne Martin-Chouly ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Inflammation ◽  
Bacterial Infections ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Inherited Disease ◽  
Bacterial Killing ◽  
Significant Enrichment ◽  
The Impact

Abstract Cystic fibrosis (CF) is an inherited disease that is characterised by susceptibility to bacterial infections and chronic lung inflammation. Recently, it was suggested that macrophages contribute to impaired host defence and excessive inflammatory responses in CF. Indeed, dysfunction attributed to CF macrophages includes decreased bacterial killing and exaggerated inflammatory responses. However, the mechanisms behind such defects have only been partially defined. MicroRNAs (miRNAs) have emerged as key regulators of several macrophage functions, including their activation, differentiation and polarisation. The goal of this study was to investigate whether miRNA dysregulation underlies the functional abnormalities of CF macrophages. MiRNA profiling of macrophages was performed, with 22 miRNAs identified as differentially expressed between CF and non-CF individuals. Among these, miR-146a was associated with significant enrichment of validated target genes involved in responses to microorganisms and inflammation. As miR-146a dysregulation has been reported in several human inflammatory diseases, we analysed the impact of increased miR-146a expression on inflammatory responses of CF macrophages. These data show that inhibition of miR-146a in lipopolysaccharide-stimulated CF macrophages results in increased interleukin-6 production, which suggests that miR-146a overexpression in CF is functional, to restrict inflammatory responses.

scholarly journals Macrophage-Derived Protein S Facilitates Apoptotic Polymorphonuclear Cell Clearance by Resolution Phase Macrophages and Supports Their Reprogramming

2018 ◽  
Vol 9 ◽  
Author(s):  
Delphine Lumbroso ◽  
Soaad Soboh ◽  
Avi Maimon ◽  
Sagie Schif-Zuck ◽  
Amiram Ariel ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Ex Vivo ◽  
Protein S ◽  
Peritoneal Macrophages ◽  
Polymorphonuclear Cells ◽  
Resolvin D1 ◽  
Resolution Of Inflammation ◽  
Arginase 1 ◽  
Anti Inflammatory

The complete resolution of inflammation requires the uptake of apoptotic polymorphonuclear cells (PMN) by local macrophages (efferocytosis) and the consequent reprogramming of the engulfing phagocytes to reparative and pro-resolving phenotypes. The tyrosine kinase receptors TYRO3, AXL, and MERTK (collectively named TAM) are fundamental mediators in regulating inflammatory responses and efferocytosis. Protein S (PROS1) is a ligand for all TAM receptors that mediates various aspects of their activity. However, the involvement of PROS1 in the resolution of inflammation is incompletely understood. Here, we report the upregulation of Pros1 in macrophages during the resolution of inflammation. Selective knockout of Pros1 in the myeloid lineage significantly downregulated macrophage pro-resolving properties. Hence, Pros1-deficient macrophages engulfed fewer apoptotic PMN remnants in vivo, and exogenous PROS1 rescued impaired efferocytosis ex vivo. Moreover, Pros1-deficient peritoneal macrophages secreted higher levels of the pro-inflammatory mediators TNFα and CCL3, while they secreted lower levels of the reparative/anti-inflammatory IL-10 following exposure to lipopolysaccharide in comparison to their WT counterparts. Moreover, Pros1-deficient macrophages expressed less of the anti-inflammatory/pro-resolving enzymes arginase-1 and 12/15-lipoxygenase and produced less of the specialized pro-resolving mediator resolvin D1. Altogether, our results suggest that macrophage-derived PROS1 is an important effector molecule in regulating the efferocytosis, maturation, and reprogramming of resolution phase macrophages, and imply that PROS1 could provide a new therapeutic target for inflammatory and fibrotic disorders.

scholarly journals RvD1 accelerates the resolution of inflammation by promoting apoptosis of the recruited macrophages via the ALX/FasL-FasR/caspase-3 signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shu-yang Xiang ◽  
Yang Ye ◽  
Qian Yang ◽  
Hao- ran Xu ◽  
Chen-xi Shen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Distress Syndrome ◽  
Inflammatory Factors ◽  
Lipid Mediator ◽  
Resolvin D1 ◽  
Resolution Of Inflammation ◽  
Inflammatory Monocytes ◽  
Endogenous Lipid ◽  
Inflammation Resolution

AbstractThe uncontrolled inflammatory response caused by a disorder in inflammation resolution is one of the reasons for acute respiratory distress syndrome (ARDS). The macrophage pool markedly expands when inflammatory monocytes, known as recruited macrophages, migrate from the circulation to the lung. The persistent presence of recruited macrophages leads to chronic inflammation in the resolution phase of inflammation. On the contrary, elimination of the recruited macrophages at the injury site leads to the rapid resolution of inflammation. Resolvin D1 (RvD1) is an endogenous lipid mediator derived from docosahexaenoic acid. Mice were administered RvD1 via the tail vein 3 and 4 days after stimulation with lipopolysaccharide. RvD1 reduced the levels of the inflammatory factors in the lung tissue, promoted the anti-inflammatory M2 phenotype, and enhanced the phagocytic function of recruited macrophages to alleviate acute lung injury. We also found that the number of macrophages was decreased in BAL fluid after treatment with RvD1. RvD1 increased the apoptosis of recruited macrophages partly via the FasL-FasR/caspase-3 signaling pathway, and this effect could be blocked by Boc-2, an ALX/PRP2 inhibitor. Taken together, our findings reinforce the concept of therapeutic targeting leading to the apoptosis of recruited macrophages. Thus, RvD1 may provide a new therapy for the resolution of ARDS.

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

2018 ◽  
Vol 17 (5) ◽  
pp. 607-615 ◽  
Author(s):  
Fiona C. Ringholz ◽  
Gerard Higgins ◽  
Aurélie Hatton ◽  
Ali Sassi ◽  
Ahmad Moukachar ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Ion Transport ◽  
Resolvin D1 ◽  
Epithelial Ion Transport

scholarly journals AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Abdominal Sepsis ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Lung Infections ◽  
Sepsis Survivors ◽  
The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

Resolvin D1 and E1 promote resolution of inflammation in rat cardiac fibroblast in vitro

2021 ◽  
Vol 48 (1) ◽  
pp. 57-66
Author(s):  
Aimeé Salas-Hernández ◽  
Claudio Espinoza-Pérez ◽  
Raúl Vivar ◽  
Jenaro Espitia-Corredor ◽  
José Lillo ◽  
...  
Keyword(s):  
Cardiac Fibroblast ◽  
Resolvin D1 ◽  
Resolution Of Inflammation

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

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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