scholarly journals Bioactive lipids-based therapeutic approach to COVID-19 and other similar infections

2021 ◽  
Author(s):  
Undurti Das
Keyword(s):  
Prostaglandin E1 ◽  
Target Cells ◽  
M2 Macrophages ◽  
Gamma Linolenic Acid ◽  
Bioactive Lipids ◽  
Lipoxin A4 ◽  
Enveloped Viruses ◽  
Cell Membrane Fluidity ◽  
Anti Inflammatory ◽  
M1 And M2 Macrophages

It is suggested that COVID-19 (coronavirus) and other enveloped viruses can be inactivated by bioactive lipids. Bioactive lipids (BALs) AA, gamma-linolenic acid (GLA), dihomo-GLA (DGLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) are precursors to anti-inflammatory metabolites prostaglandin E1, lipoxin A4, resolvins, protectins and maresins that enhance phagocytosis of macrophages and leukocytes to clear debris, enhance microbial clearance and wound healing to restore homeostasis. BALs influence cell membrane fluidity and thus, prevent SARS-CoV-2, influenza, and Arboviruses (such as Chikungunya, Dengue, Zika) to infect the target cells. BALs modulate the generation of M1 and M2 macrophages. Mesenchymal and adipose tissue-derived stem cells secrete LXA4 and other BALs to bring about their beneficial actions in COVID-19. Prostaglandin E2 (PGE2), derived from arachidonic acid, triggers generation of anti-inflammatory lipoxin A4 and thus, modulates pathogenesis of COVID-19. AA, the precursor to both PGE2 and LXA4, and thus, is suited to prevent and ameliorate COVID-19.

scholarly journals Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2

2020 ◽  
Author(s):  
Fuyu Duan ◽  
Liyan Guo ◽  
Liuliu Yang ◽  
Yuling Han ◽  
Abhimanyu Thakur ◽  
...  
Keyword(s):  
Early Stage ◽  
Synergistic Effects ◽  
Inflammatory Factors ◽  
Target Cells ◽  
Lung Cells ◽  
Alveolar Type ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Abstract Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies. Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages.

Differential expression of inflammatory and anti-inflammatory mediators by M1 and M2 macrophages after photobiomodulation with red or infrared lasers

2019 ◽  
Vol 35 (2) ◽  
pp. 337-343 ◽  
Author(s):  
Kaline de Brito Sousa ◽  
Maria Fernanda Setúbal Destro Rodrigues ◽  
Debora de Souza Santos ◽  
Raquel Agnelli Mesquita-Ferrari ◽  
Fabio Daumas Nunes ◽  
...  
Keyword(s):  
Differential Expression ◽  
Inflammatory Mediators ◽  
M2 Macrophages ◽  
Infrared Lasers ◽  
Anti Inflammatory ◽  
M1 And M2 Macrophages

scholarly journals Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyu Sun ◽  
Jike Gao ◽  
Xiang Meng ◽  
Xiaoxuan Lu ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Research Progress ◽  
Periodontal Tissue ◽  
M2 Macrophages ◽  
Molecular Signaling ◽  
Local Inflammatory Response ◽  
Anti Inflammatory ◽  
M1 Type ◽  
M1 And M2 Macrophages

Periodontitis (PD) is a common chronic infectious disease. The local inflammatory response in the host may cause the destruction of supporting periodontal tissue. Macrophages play a variety of roles in PD, including regulatory and phagocytosis. Moreover, under the induction of different factors, macrophages polarize and form different functional phenotypes. Among them, M1-type macrophages with proinflammatory functions and M2-type macrophages with anti-inflammatory functions are the most representative, and both of them can regulate the tendency of the immune system to exert proinflammatory or anti-inflammatory functions. M1 and M2 macrophages are involved in the destructive and reparative stages of PD. Due to the complex microenvironment of PD, the dynamic development of PD, and various local mediators, increasing attention has been given to the study of macrophage polarization in PD. This review summarizes the role of macrophage polarization in the development of PD and its research progress.

scholarly journals Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2

2020 ◽  
Author(s):  
Fuyu Duan ◽  
Liyan Guo ◽  
Liuliu Yang ◽  
Yuling Han ◽  
Abhimanyu Thakur ◽  
...  
Keyword(s):  
Early Stage ◽  
Synergistic Effects ◽  
Inflammatory Factors ◽  
Target Cells ◽  
Lung Cells ◽  
Alveolar Type ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Abstract Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies. Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages.

scholarly journals Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles

Blood ◽  
2008 ◽  
Vol 112 (6) ◽  
pp. 2512-2519 ◽  
Author(s):  
Jesmond Dalli ◽  
Lucy V. Norling ◽  
Derek Renshaw ◽  
Dianne Cooper ◽  
Kit-Yi Leung ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Biologically Active ◽  
Target Cells ◽  
Lipoxin A4 ◽  
Cell Recruitment ◽  
Annexin 1 ◽  
Inflammatory Protein ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Polymorphonuclear leukocyte (PMN)–derived microparticles display inhibitory properties on target cells as assessed in vitro; since PMNs contain abundant amounts of the endogenous anti-inflammatory protein annexin 1 (AnxA1), we tested here whether biologically active AnxA1 could be present in PMN-derived microparticles. PMN adhesion to human umbilical vein endothelial cell (HUVEC) monolayers led to the generation of microparticles that contained AnxA1, as detected by Western blotting, flow cytometry, and mass spectrometry analyses. Addition of these microparticles to recipient PMNs prior to flow over HUVEC monolayers significantly inhibited cell adhesion, an effect abrogated by a neutralizing anti-AnxA1 antibody, or an antibody raised against the AnxA1 receptor, that is termed lipoxin A4 receptor or ALX. Intravenous delivery of human PMN–derived microparticles markedly inhibited PMN recruitment to an air pouch inflamed with IL-1β. This anti-inflammatory effect was also dependent on endogenous AnxA1, since injection of microparticles produced from wild-type PMNs (bone marrow derived), but not from AnxA1-null PMNs, inhibited IL-1β–induced leukocyte trafficking. In conclusion, PMN-derived microparticles contain functionally active AnxA1 that confers them anti-inflammatory properties; generation of these microparticles in the microcirculation could promote inflammatory resolution by time-dependent dampening of cell recruitment.

High glucose induces donors-specific cytokine response in primary human M1 and M2 macrophages

2015 ◽  
Vol 10 (S 01) ◽  
Author(s):  
K Moganti ◽  
F Li ◽  
S Riehman ◽  
H Klüter ◽  
M Harmsen ◽  
...  
Keyword(s):  
High Glucose ◽  
Cytokine Response ◽  
M2 Macrophages ◽  
M1 And M2 Macrophages

scholarly journals VitA or VitD ameliorates bronchopulmonary dysplasia by regulating the balance between M1 and M2 macrophages

2021 ◽  
Vol 141 ◽  
pp. 111836
Author(s):  
Hong Zhen ◽  
Hongbo Hu ◽  
Guojie Rong ◽  
Xiuxiu Huang ◽  
Chang Tan ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
M2 Macrophages ◽  
M1 And M2 Macrophages

scholarly journals Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lu Wang ◽  
Yafei Rao ◽  
Xiali Liu ◽  
Liya Sun ◽  
Jiameng Gong ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Lung Inflammation ◽  
Respiratory Diseases ◽  
Inflammatory Responses ◽  
The Other ◽  
Target Cells ◽  
Administration Route ◽  
Toll Like Receptor ◽  
Administration Routes ◽  
Anti Inflammatory

Abstract Background Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. Results In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not. Conclusion The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

scholarly journals Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?

2021 ◽  
Vol 22 (8) ◽  
pp. 4207
Author(s):  
Nikola Tułowiecka ◽  
Dariusz Kotlęga ◽  
Andrzej Bohatyrewicz ◽  
Małgorzata Szczuko
Keyword(s):  
Ischemic Stroke ◽  
Cardiovascular Diseases ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
The Body ◽  
Brain Barrier ◽  
Lipoxin A4 ◽  
Stroke Treatment ◽  
Blood Brain ◽  
Anti Inflammatory

Introduction: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins—pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. Aim: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. Material and Methods: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: ‘stroke and lipoxin’ and ‘stroke and atherosclerosis’, resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. Results: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood–brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1β, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog—BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood–brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. Conclusions: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.

scholarly journals Bioactive Lipids of Marine Microalga Chlorococcum sp. SABC 012504 with Anti-Inflammatory and Anti-thrombotic Activities

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 28
Author(s):  
Katie Shiels ◽  
Alexandros Tsoupras ◽  
Ronan Lordan ◽  
Constantina Nasopoulou ◽  
Ioannis Zabetakis ◽  
...  
Keyword(s):  
Essential Fatty Acids ◽  
Lipid Fraction ◽  
Platelet Activating Factor ◽  
Human Platelets ◽  
Bioactive Molecules ◽  
Bioactive Lipids ◽  
Alternative Source ◽  
Lipid Fractions ◽  
Anti Inflammatory

Microalgae are at the start of the food chain, and many are known producers of a significant amount of lipids with essential fatty acids. However, the bioactivity of microalgal lipids for anti-inflammatory and antithrombotic activities have rarely been investigated. Therefore, for a sustainable source of the above bioactive lipids, the present study was undertaken. The total lipids of microalga Chlorococcum sp., isolated from the Irish coast, were fractionated into neutral-, glyco-, and phospho-lipids, and were tested in vitro for their anti-inflammatory and antithrombotic activities. All tested lipid fractions showed strong anti-platelet-activating factor (PAF) and antithrombin activities in human platelets (half maximal inhibitory concentration (IC50) values ranging ~25–200 μg of lipid) with the highest activities in glyco- and phospho-lipid fractions. The structural analysis of the bioactive lipid fraction-2 revealed the presence of specific sulfoquinovosyl diacylglycerols (SQDG) bioactive molecules and the HexCer-t36:2 (t18:1/18:1 and 18:2/18:0) cerebrosides with a phytosphingosine (4-hydrosphinganine) base, while fraction-3 contained bioactive phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecules. These novel bioactive lipids of Chlorococcum sp. with putative health benefits may indicate that marine microalgae can be a sustainable alternative source for bioactive lipids production for food supplements and nutraceutical applications. However, further studies are required towards the commercial technology pathways development and biosafety analysis for the use of the microalga.

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