scholarly journals Neuroimmune Response in Natural Preclinical Scrapie after Dexamethasone Treatment

2020 ◽  
Vol 21 (16) ◽  
pp. 5779
Author(s):  
Isabel M. Guijarro ◽  
Moisés Garcés ◽  
Belén Marín ◽  
Alicia Otero ◽  
Tomás Barrio ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Target Cells ◽  
Dexamethasone Treatment ◽  
In Vivo Animal Model ◽  
Advanced Stages ◽  
Natural Scrapie ◽  
Potential Failure ◽  
Anti Inflammatory

A recently published report on chronic dexamethasone treatment for natural scrapie supported the hypothesis of the potential failure of astroglia in the advanced stage of disease. Herein, we aimed to extend the aforementioned study on the effect of this anti-inflammatory therapy to the initial phase of scrapie, with the aim of elucidating the natural neuroinflammatory process occurring in this neurodegenerative disorder. The administration of this glucocorticoid resulted in an outstanding reduction in vacuolation and aberrant protein deposition (nearly null), and an increase in glial activation. Furthermore, evident suppression of IL-1R and IL-6 and the exacerbation of IL-1α, IL-2R, IL-10R and IFNγR were also demonstrated. Consequently, the early stage of the disease is characterized by an intact neuroglial response similar to that of healthy individuals attempting to re-establish homeostasis. A complex network of neuroinflammatory markers is involved from the very early stages of this prion disease, which probably becomes impaired in the more advanced stages. The in vivo animal model used herein provides essential observations on the pathogenesis of natural scrapie, as well as the possibility of establishing neuroglia as potential target cells for anti-inflammatory therapy.

scholarly journals Neuroimmune Response Mediated by Cytokines in Natural Scrapie after Chronic Dexamethasone Treatment

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 204
Author(s):  
Isabel M. Guijarro ◽  
Moisés Garcés ◽  
Pol Andrés-Benito ◽  
Belén Marín ◽  
Alicia Otero ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Global Approach ◽  
Profile Data ◽  
Dexamethasone Treatment ◽  
New Approach ◽  
Complex Interactions ◽  
Natural Scrapie ◽  
Anti Inflammatory

The actual role of prion protein-induced glial activation and subsequent cytokine secretion during prion diseases is still incompletely understood. The overall aim of this study is to assess the effect of an anti-inflammatory treatment with dexamethasone on different cytokines released by neuroglial cells that are potentially related to neuroinflammation in natural scrapie. This study emphasizes the complex interactions existent among several pleiotropic neuromodulator peptides and provides a global approach to clarify neuroinflammatory processes in prion diseases. Additionally, an impairment of communication between microglial and astroglial populations mediated by cytokines, mainly IL-1, is suggested. The main novelty of this study is that it is the first one assessing in situ neuroinflammatory activity in relation to chronic anti-inflammatory therapy, gaining relevance because it is based on a natural model. The cytokine profile data would suggest the activation of some neurotoxicity-associated route. Consequently, targeting such a pathway might be a new approach to modify the damaging effects of neuroinflammation.

Design and characterization of a cleavage-resistant Annexin A1 mutant to control inflammation in the microvasculature

Blood ◽  
2010 ◽  
Vol 116 (20) ◽  
pp. 4288-4296 ◽  
Author(s):  
Magali Pederzoli-Ribeil ◽  
Francesco Maione ◽  
Dianne Cooper ◽  
Adam Al-Kashi ◽  
Jesmond Dalli ◽  
...  
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Early Stage ◽  
Leukocyte Adhesion ◽  
Formyl Peptide Receptor ◽  
Annexin A1 ◽  
Formyl Peptide ◽  
Anti Inflammatory ◽  
Human Polymorphonuclear Leukocytes

Abstract Human polymorphonuclear leukocytes adhesion to endothelial cells during the early stage of inflammation leads to cell surface externalization of Annexin A1 (AnxA1), an effector of endogenous anti-inflammation. The antiadhesive properties of AnxA1 become operative to finely tune polymorphonuclear leukocytes transmigration to the site of inflammation. Membrane bound proteinase 3 (PR3) plays a key role in this microenvironment by cleaving the N terminus bioactive domain of AnxA1. In the present study, we generated a PR3-resistant human recombinant AnxA1—named superAnxA1 (SAnxA1)—and tested its in vitro and in vivo properties in comparison to the parental protein. SAnxA1 bound and activated formyl peptide receptor 2 in a similar way as the parental protein, while showing a resistance to cleavage by recombinant PR3. SAnxA1 retained anti-inflammatory activities in the murine inflamed microcirculation (leukocyte adhesion being the readout) and in skin trafficking model. When longer-lasting models of inflammation were applied, SAnxA1 displayed stronger anti-inflammatory effect over time compared with the parental protein. Together these results indicate that AnxA1 cleavage is an important process during neutrophilic inflammation and that controlling the balance between AnxA1/PR3 activities might represent a promising avenue for the discovery of novel therapeutic approaches.

Cytokine signaling during myocardial infarction: sequential appearance of IL-1 beta and IL-6

1995 ◽  
Vol 269 (2) ◽  
pp. R229-R235 ◽  
Author(s):  
I. Guillen ◽  
M. Blanes ◽  
M. J. Gomez-Lechon ◽  
J. V. Castell
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Protein Synthesis ◽  
Proinflammatory Cytokines ◽  
Early Stage ◽  
Myocardial Infarct ◽  
Cytokine Signaling ◽  
Target Cells ◽  
Necrosis Factor Alpha

The purpose of this study was to investigate the significance of the sequential changes in proinflammatory cytokines observed in the plasma of patients early after myocardial infarct: a rise in interleukin (IL)-1 beta (308 +/- 126 vs. 141 +/- 78 pg/ml, P < 0.01) between 0 and 2 h followed by an IL-6 peak (49 +/- 24 vs. 14.5 +/- 13 pg/ml, P < 0.01) 4-9 h later. No significant changes in tumor necrosis factor-alpha (TNF-alpha) were observed at this early stage. The linkage between IL-1 beta and IL-6 secretions is supported by 1) the ability of patient's plasma drawn early after myocardial infarction to induce IL-6 mRNA and protein synthesis in cells that may be potential targets in vivo (fibroblasts and endothelial cells), 2) suppression of this activity by antibodies against IL-1 beta, and 3) a delay between IL-1 beta and IL-6 peaks in vivo (4-9 h), which is similar to the time required for maximal IL-6 production in IL-1 beta stimulated target cells in vitro (6 h). This sequential signaling might serve as the basis for an amplification mechanism of proinflammatory cytokines. In fact, a much greater synthesis of C-reactive protein was observed in hepatocytes when stimulated with conditioned medium of fibroblasts or endothelial cells that had previously been incubated with plasma of patients. The results of our work strongly suggest that, by inducing IL-6 in potential target cells, IL-1 beta could act as the primary, but indirect, signal that stimulates acute-phase protein synthesis after myocardial injury.

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 Nigella sativa and Its Active Compound, Thymoquinone, Accelerate Wound Healing in an In Vivo Animal Model: A Comprehensive Review

2020 ◽  
Vol 17 (11) ◽  
pp. 4160 ◽  
Author(s):  
Nusaibah Sallehuddin ◽  
Abid Nordin ◽  
Ruszymah Bt Hj Idrus ◽  
Mh Busra Fauzi
Keyword(s):  
Wound Healing ◽  
Nigella Sativa ◽  
Healing Process ◽  
Skin Wound ◽  
Tissue Growth ◽  
Inclusion Criteria ◽  
Skin Wound Healing ◽  
In Vivo Animal Model ◽  
Anti Inflammatory

Nigella sativa (NS) has been reported to have a therapeutic effect towards skin wound healing via its anti-inflammatory, tissue growth stimulation, and antioxidative properties. This review examines all the available studies on the association of Nigella sativa (NS) and skin wound healing. The search was performed in Medline via EBSCOhost and Scopus databases to retrieve the related papers released between 1970 and March 2020. The principal inclusion criteria were original article issued in English that stated wound healing criteria of in vivo skin model with topically applied NS. The search discovered 10 related articles that fulfilled the required inclusion criteria. Studies included comprise different types of wounds, namely excisional, burn, and diabetic wounds. Seven studies unravelled positive results associated with NS on skin wound healing. Thymoquinone has anti-inflammatory, antioxidant, and antibacterial properties, which mainly contributed to wound healing process.

Delivery of Ferulic Acid with PEGylated DiphenylalanineBased Nanoparticles for the Treatment of Arthritis in Early Stage

2021 ◽  
Vol 17 (3) ◽  
pp. 357-368
Author(s):  
Liming He ◽  
Yingchun Zeng ◽  
Xianyan Qin ◽  
Lihua Pan ◽  
Tao Chen ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Early Stage ◽  
Oxygen Species ◽  
Poly Ethylene Glycol ◽  
Anti Inflammatory ◽  
Poly Ethylene ◽  
Favorable Safety ◽  
Arthritic Joints ◽  
Glycol Methyl Ether

Ferulic acid (FA), an active component extracted from Chinese medicine, shows excellent anti-inflammatory properties and favorable safety in various animal models. However, the application of FA as an anti-inflammatory drug is hindered by its instability and short half-life in vivo . In this paper, we synthesize PEGylated diphenylalanine nanoparticles by using glutaraldehyde (GTA) as a cross-linker of diphenylalanine NH2 -Phe–Phe-COOH and poly(ethylene glycol) methyl ether amine (PEG5k -NH2). The PEGylated Phe–Phe nanoparticles are used to deliver FA for the treatment of Rheumatoid arthritis (RA). We find that the FA-loaded PEGylated Phe–Phe nanoparticles are biocompatible and inhibit the production of reactive oxygen species (ROS) from cells effectively. After being intravenously administrated in vivo , the FA-loaded PEGylated Phe–Phe nanoparticles show prolonged circulation time and accumulate in arthritic joints. More importantly, we show that the pre-arthritis treatment with the FA-loaded PEGylated Phe–Phe nanoparticles can significantly block the progression of RA.

scholarly journals Amla (Emblica officinalisGaertn.) extract inhibits lipopolysaccharide-induced procoagulant and pro-inflammatory factors in cultured vascular endothelial cells

2013 ◽  
Vol 110 (12) ◽  
pp. 2201-2206 ◽  
Author(s):  
Theertham Pradyumna Rao ◽  
Takayuki Okamoto ◽  
Nobuyuki Akita ◽  
Tatsuya Hayashi ◽  
Naomi Kato-Yasuda ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Inflammatory Factors ◽  
Target Cells ◽  
Fruit Extract ◽  
Leucocyte Adhesion ◽  
Anti Inflammatory

Amla (Emblica officinalisGaertn.) has been used for many centuries in traditional Indian Ayurvedic formulations for the prevention and treatment of many inflammatory diseases. The present study evaluated the anti-inflammatory and anticoagulant properties of amla fruit extract. The amla fruit extract potentially and significantly reduced lipopolysaccharide (LPS)-induced tissue factor expression and von Willebrand factor release in human umbilical vein endothelial cells (HUVEC)in vitroat clinically relevant concentrations (1–100 μg/ml). In a leucocyte adhesion model of inflammation, it also significantly decreased LPS-induced adhesion of human monocytic cells (THP-1) to the HUVEC, as well as reduced the expression of endothelial-leucocyte adhesion molecule-1 (E-selectin) in the target cells. In addition, thein vivoanti-inflammatory effects were evaluated in a LPS-induced endotoxaemia rat model. Oral administration of the amla fruit extract (50 mg/kg body weight) significantly decreased the concentrations of pro-inflammatory cytokines, TNF-α and IL-6 in serum. These results suggest that amla fruit extract may be an effective anticoagulant and anti-inflammatory agent.

scholarly journals Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Xia ◽  
Yitong Liu ◽  
Guiyang Xia ◽  
Yi Liu ◽  
Sheng Lin ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Critical Role ◽  
Isoquinoline Alkaloid ◽  
Inflammatory Factors ◽  
Skin Wound Healing ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Macrophages play a critical role in innate and adaptive immunity, and the regulation of macrophage function in inflammatory disease treatment has been widely studied. Litsea cubeba is an important Chinese medicinal plant used for the treatment of inflammatory diseases. However, the inflammatory bioactive ingredients in L. cubeba and underlying molecular mechanisms are poorly understood. Herein, we first obtained and elucidated a novel isoquinoline alkaloid, Litcubanine A (LA), from L. cubeba. An in vitro study indicated that LA could significantly inhibit LPS-induced activation of inflammatory macrophages via the NF-κB pathway, leading to the decrease of inflammatory factors including iNOS, TNF-α, and IL-1β. Moreover, LA showed an inhibiting effect on the expression of NO in macrophages by directly binding to iNOS protein. Molecular simulation docking also demonstrated that active LA created an interaction with GLU 371 residue of iNOS via attractive charge derived from the N→O group, revealing its highly selective inhibition toward iNOS. By using the IκK inhibitor and iNOS inhibitor, these two regulatory targets of LA on inflammatory macrophages were verified in vitro. Finally, by using a caudal fin resection model in zebrafish larvae, and the skin wound healing model in mice, we proved in vivo that LA down-regulated the secretion of local inflammatory factors by inhibiting macrophage recruitment and activation at the early stage of the injury. Collectively, our study demonstrated that the novel isoquinoline alkaloid LA suppresses LPS-induced activation of inflammatory macrophages by modulating the NF-κB pathway, suggesting that inflammatory macrophage activation pathway is an effective target for inflammation treatment, and LA is a new pharmacophore for the development of novel and effective anti-inflammatory agents to regulate local macrophages.

scholarly journals Delivery of Ferulic Acid with PEGylated Diphenylalanine Nanoparticles for Pre-arthritis Therapy

2021 ◽  
Author(s):  
Liming He ◽  
Yingchun Zeng ◽  
Xianyan Qin ◽  
Lihua Pan ◽  
Tao Chen ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Late Stage ◽  
Therapeutic Efficacy ◽  
Inflammatory Diseases ◽  
Early Stage ◽  
Therapeutic Outcomes ◽  
Anti Inflammatory ◽  
Poly Ethylene ◽  
Arthritic Joints

Abstract Background: In the therapy of rheumatoid arthritis (RA), treatment starting at the late stage of disease is probably associated with a worse disease outcome. Thus, blocking the RA developments at the early stage of inflammation with efficacious and safe agents might present a promising strategy. Ferulic acid (FA), a safe and active component extracted from Chinese medicine, shows excellent anti-inflammatory properties in various inflammatory diseases. However, the application of FA as an anti-inflammatory drug is hindered by its instability and short half-life in vivo. The aim of this study is to design a feasible drug delivery system to improve the therapeutic efficacy of FA in the treatment of RA and investigate whether treatment initiated at early stage of arthritis would effectively prevent the development of arthritis.Method: A diphenylalanine-based nanoparticle was constructed by the self-stacking of NH2-Phe-Phe-COOH and poly (ethylene glycol) methyl ether amine (PEG5k-NH2) using the glutaraldehyde (GTA) as a cross-linker. The therapeutic outcomes of treatment using FA-loaded PEGylated Phe-Phe nanoparticles were explored at both pre-arthritis stage and fully-developed arthritis stage. Results: We find that the FA-loaded PEGylated Phe-Phe nanoparticles are biocompatible and could effectively inhibit the production of reactive oxygen species in inflammatory condition. After being intravenously administrated in vivo, the FA-loaded PEGylated Phe-Phe nanoparticles show prolonged circulation time and enhanced accumulation in arthritic joints. More importantly, the pre-arthritis treatment with the FA-loaded PEGylated Phe-Phe nanoparticles can significantly block the progression of RA compared with treatment started at the late stage of arthritis.Conclusions: Our results demonstrated FA-loaded PEGylated Phe-Phe nanoparticles could greatly improve the therapeutic efficacy of FA and ultimately prevent the progression of arthritis in a low activity when applied in pre-arthritis phase. This therapeutic outcome confirmed the treatment initiated in very early disease phases is effective to prevent arthritis progression to full-blown disease.

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