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.

Role of the Specialized Pro-resolving Mediator Resolvin D1 in Hashimotoʼs Thyroiditis

2021 ◽  
Author(s):  
Jing Song ◽  
Rongxin Sun ◽  
Yuanyuan Zhang ◽  
Ying Fu ◽  
Dong Zhao
Keyword(s):  
Thyroid Autoimmunity ◽  
Thyroid Stimulating Hormone ◽  
Inflammatory Factors ◽  
Thyroid Peroxidase ◽  
Sensitivity Index ◽  
Resolvin D1 ◽  
Thyroid Peroxidase Antibody ◽  
Thyroglobulin Antibody ◽  
Inflammation Resolution

Abstract Objective Resolvins are produced by the catabolism of polyunsaturated fatty acids (PUFAs) and play vital roles in inflammation resolution. Resolvins have been associated with autoimmune disorders. This study aimed to measure the level of Resolvin D1 (RVD1) in the serum of Hashimoto's thyroiditis (HT) patients and healthy controls (HCs) and to further analyse its correlation with thyroid autoantibodies and inflammatory factors. Methods Sixty-three participants were recruited, namely, 30 untreated HT patients and 33 sex- and age-matched HCs. Serum RVD1 and inflammatory chemokine (MCP-1 and IP-10) levels were measured by ELISA according to the manufacturer’s protocol. Serum total T3 (TT3), TT4, free T3 (FT3), FT4, thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and thyroid-stimulating hormone (TSH) levels were measured using an electrochemiluminescence immunoassay. Thyroid homeostasis parameters, including the thyroid secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD), Jostel’s TSH index (TSHI) and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated. Results Serum RVD1 levels in HT patients (134.76, 85.35–201.36 pg/mL) were significantly lower than those in HCs (187.64, 131.01–326.85 pg/mL) (P=0.004). As the TPOAb level increased, the RVD1 level showed a decreasing trend (P for trend=0.002). Both multinomial and ordinal logistics analyses revealed that serum RVD1 levels were negatively correlated with TPOAb levels in the adjusted models. Moreover, RVD1 showed a negative correlation with the inflammatory chemokine IP-1 0 (r=–0.276, P=0.034), TSHI (r=–0.269, P=0.036) and TTSI (r=–0.277, P=0.031). Conclusions Thyroid autoimmunity may be associated with low levels of RVD1. Decreased RVD1 levels indicate impaired resolution of inflammation in HT patients.

scholarly journals Roles of Specialized Pro-Resolving Lipid Mediators in Autophagy and Inflammation

2020 ◽  
Vol 21 (18) ◽  
pp. 6637 ◽  
Author(s):  
Antonio Recchiuti ◽  
Elisa Isopi ◽  
Mario Romano ◽  
Domenico Mattoscio
Keyword(s):  
Inflammatory Response ◽  
Cytokine Production ◽  
Lipid Mediators ◽  
Tissue Homeostasis ◽  
Leukocyte Infiltration ◽  
Catabolic Pathway ◽  
Resolution Of Inflammation ◽  
Endogenous Lipid ◽  
Inflammation Resolution ◽  
Cellular Components

Autophagy is a catabolic pathway that accounts for degradation and recycling of cellular components to extend cell survival under stress conditions. In addition to this prominent role, recent evidence indicates that autophagy is crucially involved in the regulation of the inflammatory response, a tightly controlled process aimed at clearing the inflammatory stimulus and restoring tissue homeostasis. To be efficient and beneficial to the host, inflammation should be controlled by a resolution program, since uncontrolled inflammation is the underlying cause of many pathologies. Resolution of inflammation is an active process mediated by a variety of mediators, including the so-called specialized pro-resolving lipid mediators (SPMs), a family of endogenous lipid autacoids known to regulate leukocyte infiltration and activities, and counterbalance cytokine production. Recently, regulation of autophagic mechanisms by these mediators has emerged, uncovering unappreciated connections between inflammation resolution and autophagy. Here, we summarize mechanisms of autophagy and resolution, focusing on the contribution of autophagy in sustaining paradigmatic examples of chronic inflammatory disorders. Then, we discuss the evidence that SPMs can restore dysregulated autophagy, hypothesizing that resolution of inflammation could represent an innovative approach to modulate autophagy and its impact on the inflammatory response.

scholarly journals Harnessing lipid signaling pathways to target specialized pro-angiogenic neutrophil subsets for regenerative immunotherapy

2020 ◽  
Vol 6 (44) ◽  
pp. eaba7702
Author(s):  
T. C. Turner ◽  
M. C. P. Sok ◽  
L. A. Hymel ◽  
F. S. Pittman ◽  
W. Y. York ◽  
...  
Keyword(s):  
Single Cell ◽  
Neutrophil Infiltration ◽  
Sterile Inflammation ◽  
Lipid Mediator ◽  
Cell Phenotype ◽  
Resolvin D1 ◽  
Flow Cytometry Data ◽  
Cell Flow Cytometry ◽  
Inflammation Resolution ◽  
Window Chamber

To gain insights into neutrophil heterogeneity dynamics in the context of sterile inflammation and wound healing, we performed a pseudotime analysis of single-cell flow cytometry data using the spanning-tree progression analysis of density-normalized events algorithm. This enables us to view neutrophil transitional subsets along a pseudotime trajectory and identify distinct VEGFR1, VEGFR2, and CXCR4 high-expressing pro-angiogenic neutrophils. While the proresolving lipid mediator aspirin-triggered resolvin D1 (AT-RvD1) has a known ability to limit neutrophil infiltration, our analysis uncovers a mode of action in which AT-RvD1 leads to inflammation resolution through the selective reprogramming toward a therapeutic neutrophil subset. This accumulation leads to enhanced vascular remodeling in the skinfold window chamber and a proregenerative shift in macrophage and dendritic cell phenotype, resulting in improved wound closure after skin transplantation. As the targeting of functional immune subsets becomes the key to regenerative immunotherapies, single-cell pseudotime analysis tools will be vital in this field.

scholarly journals Hydrogen-Rich Saline Attenuates Brain Injury Induced by Cardiopulmonary Bypass and Inhibits Microvascular Endothelial Cell Apoptosis Via the PI3K/Akt/GSK3β Signaling Pathway in Rats

2017 ◽  
Vol 43 (4) ◽  
pp. 1634-1647 ◽  
Author(s):  
Keyan Chen ◽  
Nan Wang ◽  
Yugang Diao ◽  
Wanwei Dong ◽  
YingJie Sun ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Brain Tissue ◽  
Caspase 3 ◽  
Cell Structure ◽  
Regulatory Gene ◽  
Open Heart Surgery ◽  
Inflammatory Factors ◽  
Microvascular Endothelial

Background/Aims: Cardiopulmonary bypass (CPB) is prone to inducing brain injury during open heart surgery. A hydrogen-rich solution (HRS) can prevent oxidation and apoptosis, and inhibit inflammation. This study investigated effects of HRS on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3β signaling pathway. Methods: A rat CPB model and an in vitro cell hypoxia model were established. After HRS treatment, Rat behavior was measured using neurological deficit score; Evans blue (EB) was used to assess permeability of the blood-brain barrier (BBB); HE staining was used to observe pathological changes; Inflammatory factors and brain injury markers were detected by ELISA; the PI3K/Akt/GSK3β pathway-related proteins and apoptosis were assessed by western blot, immunohistochemistry and qRT –PCR analyses of brain tissue and neurons. Results: After CPB, brain tissue anatomy was disordered, and cell structure was abnormal. Brain tissue EB content increased. There was an increase in the number of apoptotic cells, an increase in expression of Bax and caspase-3, a decrease in expression of Bcl2, and increases in levels of Akt, GSK3β, P-Akt, and P-GSK3β in brain tissue. HRS treatment attenuated the inflammatory reaction ,brain tissue EB content was significantly reduced and significantly decreased expression levels of Bax, caspase-3, Akt, GSK3β, P-Akt, and P-GSK3β in the brain. After adding the PI3K signaling pathway inhibitor, LY294002, to rat cerebral microvascular endothelial cells (CMECs), HRS could reduce activated Akt expression and downstream regulatory gene phosphorylation of GSK3β expression, and inhibit CMEC apoptosis. Conclusion: The PI3K/Akt/GSK3β signaling pathway plays an important role in the mechanism of CPB-induced brain injury. HRS can reduce CPB-induced brain injury and inhibit CMEC apoptosis through the PI3K/Akt/GSK3β signaling pathway.

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 Geniposide Combined With Notoginsenoside R1 Attenuates Inflammation and Apoptosis in Atherosclerosis via the AMPK/mTOR/Nrf2 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyu Liu ◽  
Yuling Xu ◽  
Saibo Cheng ◽  
Xinghong Zhou ◽  
Fenghua Zhou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Caspase 3 ◽  
Blood Lipid ◽  
Stress Factors ◽  
Inflammatory Factors ◽  
Lipid Levels ◽  
Nrf2 Signaling Pathway ◽  
Blood Lipid Levels

Inflammation and apoptosis of vascular endothelial cells play a key role in the occurrence and development of atherosclerosis (AS), and the AMPK/mTOR/Nrf2 signaling pathway plays an important role in alleviating the symptoms of AS. Geniposide combined with notoginsenoside R1 (GN combination) is a patented supplement for the prevention and treatment of AS. It has been proven to improve blood lipid levels and inhibit the formation of AS plaques; however, it is still unclear whether GN combination can inhibit inflammation and apoptosis in AS by regulating the AMPK/mTOR/Nrf2 signaling pathway and its downstream signals. Our results confirmed that the GN combination could improve blood lipid levels and plaque formation in ApoE−/− mice fed with a high-fat diet (HFD), inhibit the secretion of serum inflammatory factors and oxidative stress factors. It also decreased the expression of pyrin domain containing protein 3 (NLRP3) inflammasome-related protein and Bax/Bcl2/caspase-3 pathway-related proteins. At the same time, the GN combination could also inhibit the H2O2-induced inflammatory response and apoptosis of human umbilical vein endothelial cells (HUVECs), which is mainly related to the activation of the AMPK/mTOR pathway by GN combination, which in turn induces the activation of Nrf2/HO-1 signal. In addition, the above phenomenon could be significantly reversed by dorsomorphin. Therefore, our experiments proved for the first time that the GN combination can effectively inhibit AS inflammation and apoptosis by activating the AMPK/mTOR/Nrf2 signaling pathway to inhibit the NLRP3 inflammasome and Bax/Bcl2/caspase-3 pathway.

Resolution of Inflammation by Resolvin D1 Is Essential for Peroxisome Proliferator–activated Receptor-γ–mediated Analgesia during Postincisional Pain Development in Type 2 Diabetes

2015 ◽  
Vol 123 (6) ◽  
pp. 1420-1434 ◽  
Author(s):  
Takayuki Saito ◽  
Maiko Hasegawa-Moriyama ◽  
Tae Kurimoto ◽  
Tomotsugu Yamada ◽  
Eichi Inada ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Healing Process ◽  
Lipid Mediator ◽  
Wound Healing Process ◽  
Peroxisome Proliferator ◽  
Resolvin D1 ◽  
Resolution Of Inflammation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Analgesic Effects ◽  
Pparγ Agonist

Abstract Background The wound healing process following acute inflammation after surgery is impaired in diabetes. Altered macrophage functions are linked to delayed tissue repair and pain development in diabetes. Although peroxisome proliferator–activated receptor (PPAR)-γ agonists are used to treat diabetes, their postoperative analgesic effects in diabetes have not been evaluated. Methods The PPARγ agonist rosiglitazone (rosi) was injected at the incision site of diabetic (db/db) mice with resolvin (Rv) D1, a lipid mediator involved in resolution of inflammation. Pain-related behavior, neutrophil infiltration, phagocytosis, and macrophage polarity were assessed for 7 days postoperatively. Results Rosiglitazone and RvD1 alleviated mechanical hyperalgesia in db/db (db) mice, whereas rosiglitazone alone did not alter mechanical thresholds on days 4 (db rosi + RvD1 vs. db rosi: 0.506 ± 0.106 vs. 0.068 ± 0.12) and 7 (0.529 ± 0.184 vs. 0.153 ± 0.183) after incision (n = 10 per group). In control m/m mice, the rosiglitazone-induced analgesic effects were reversed by knockdown with arachidonate 5-lipoxygenase small interfering RNA, but these were restored by addition of RvD1. In db/db mice treated with rosiglitazone and RvD1, local infiltration of neutrophils was markedly reduced, with an associated decrease in total TdT-mediated dUTP nick-end labeling cells. Acceleration of rosiglitazone-induced phenotype conversion of infiltrated macrophages from M1 to M2 was impaired in db/db mice, but it was effectively restored by RvD1 in db/db wounds. Conclusions In diabetes, exogenous administration of RvD1 is essential for PPARγ-mediated analgesia during development of postincisional pain. Resolution of inflammation accelerated by RvD1 might promote PPARγ-mediated macrophage polarization to the M2 phenotype.

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