scholarly journals Induction of Golli-MBP Expression in CNS Macrophages During Acute LPS-Induced CNS Inflammation and Experimental Autoimmune Encephalomyelitis (EAE)

2007 ◽  
Vol 7 ◽  
pp. 112-120 ◽  
Author(s):  
Tracey L. Papenfuss ◽  
J. Cameron Thrash ◽  
Patricia E. Danielson ◽  
Pamela E. Foye ◽  
Brian S. Hllbrush ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Cell Type ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Cell Type Specific ◽  
Candidate Molecule ◽  
Experimental Autoimmune

Microglia are the tissue macrophages of the CNS. Microglial activation coupled with macrophage infiltration is a common feature of many classic neurodegenerative disorders. The absence of cell-type specific markers has confounded and complicated the analysis of cell-type specific contributions toward the onset, progression, and remission of neurodegeneration. Molecular screens comparing gene expression in cultured microglia and macrophages identified Golli-myelin basic protein (MBP) as a candidate molecule enriched in peripheral macrophages.In situhybridization analysis of LPS/IFNg and experimental autoimmune encephalomyelitis (EAE)–induced CNS inflammation revealed that only a subset of CNS macrophages express Golli-MBP. Interestingly, the location and morphology of Golli-MBP+ CNS macrophages differs between these two models of CNS inflammation. These data demonstrate the difficulties of extendingin vitroobservations toin vivobiology and concretely illustrate the complex heterogeneity of macrophage activation states present in region- and stage-specific phases of CNS inflammation. Taken altogether, these are consistent with the emerging picture that the phenotype of CNS macrophages is actively defined by their molecular interactions with the CNS microenvironment.

scholarly journals Schistosomiasis Decreases Central Nervous System Inflammation and Alters the Progression of Experimental Autoimmune Encephalomyelitis

2003 ◽  
Vol 71 (9) ◽  
pp. 4996-5004 ◽  
Author(s):  
Anne Camille La Flamme ◽  
Kate Ruddenklau ◽  
B. Thomas Bäckström
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Th2 Response ◽  
Cns Inflammation ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
Experimental Autoimmune

ABSTRACT A preestablished infection with the parasitic helminth, Schistosoma mansoni, significantly reduced the incidence and delayed the onset of experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. The altered disease progression was not solely due to the induction of a strong Th2 response, since intraperitoneal injection of schistosome eggs did not affect disease development. MOG-specific gamma interferon (IFN-γ), nitric oxide, and tumor necrosis factor alpha production by splenocytes was significantly reduced in schistosome-infected mice compared to uninfected mice. However, similar levels of interleukin-10 (IL-10) were produced in an antigen-specific manner, suggesting that the induction of antigen-specific responses was not inhibited. Analysis of in vivo cytokine production by real-time PCR indicated that IL-12p40, but not IFN-γ, transcript levels were dramatically reduced in the spinal cords of schistosome-infected, MOG-immunized mice. Furthermore, analysis of the cellular composition of the spinal cords and brains revealed that a preestablished infection with S. mansoni decreased central nervous system (CNS) inflammation, particularly of macrophages and CD4 T cells. These results suggest that schistosomiasis may negatively regulate the onset of EAE by downregulating the production of proinflammatory cytokines and altering CNS inflammation.

scholarly journals Σχεδιασμός, σύνθεση και αξιολόγηση νανοσωματιδίων με εγκλωβισμό πεπτιδίων των πρωτεινών της μυελίνης

2021 ◽  
Author(s):  
Ηρώ Τριανταφυλλάκου
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Glycolic Acid ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Το αντικείμενο της παρούσας ΔΔ ήταν η ανάπτυξη πολυμερικών νανοσωματιδίων με εγκλωβισμένα πεπτιδικά ανάλογα που εμπλέκονται στην εμφάνιση και εξέλιξη της σκλήρυνσης κατά πλάκας (ΣΚΠ, Multiple Sclerosis, MS), καθώς και η βιολογική αξιολόγηση αυτών. Συγκεκριμένα, αναπτύχθηκαν σωματίδια πολυ(γλυκολικού-γαλακτικού) οξέος [poly(lactic-co-glycolic) acid, PLGA] με εγκλωβισμένα πεπτίδια με βάση τον επίτοπο 35-55 της μυελικής γλυκοπρωτεΐνης των ολιγοδενδριτών (Myelin Oligodendrocyte Glycoprotein, ΜΟG) με βάση την αλληλουχία που συναντάται στους μύες (rMOG), συζευγμένα ή μη με μόρια σακχαριτών. Η σύζευξη των πεπτιδικών αναλόγων με μόρια σακχαριτών όπως η μαννόζη και η γλυκοζαμίνη στόχευσε στην πιθανή αλληλεπίδραση με τους υποδοχείς μαννόζης που βρίσκονται στα δενδριτικά κύτταρα, κύρια αντιγονοπαρουσιαστικά κύτταρα που εμπλέκονται στην ΣΚΠ, με τους οποίους υποδοχείς παρουσιάζουν ισχυρή προσδετική ικανότητα και με σκοπό την ανάπτυξη ανοσοανοχής απέναντι στην νόσο.Η διατριβή περιλαμβάνει τον σχεδιασμό και την ανάπτυξη PLGA νανοσωματιδίων που θα φέρουν εγκλωβισμένα τα πεπτιδικά ανάλογα, παρέχοντας αυξημένη σταθερότητα στα πεπτιδικά ανάλογα και παρέχοντας την δυνατότητα βραδείας αποδέσμευσης από την πολυμερική μήτρα. Τα νανοσωματίδια που αναπτύχθηκαν μελετήθηκαν ως προς τα φυσικοχημικά τους χαρακτηριστικά ώστε να βελτιστοποιηθεί η μεθοδολογία σύνθεσης. Επιπλέον, πραγματοποιήθηκε μελέτη της βραδείας αποδέσμευσης και ποσοτικός προσδιορισμός τόσο της αρχικά εγκλωβισμένης ουσίας όσο και της ημερήσιας αποδέσμευσης σε φυσιολογικό ορό in vitro. Τέλος, τα συντεθειμένα νανοσωματίδια αξιολογήθηκαν βιολογικά in vivo στο πειραματικό μοντέλο της ΣΚΠ, την πειραματική αυτοάνοση εγκεφαλομυελίτιδα (Experimental Autoimmune Encephalomyelitis, EAE) με χρήση δύο μοντέλων ανοσοποίησης, προφυλακτικού και θεραπευτικού σε θηλυκούς μύες του γένους C57BL/6. Οι ιστοί που ελήφθησαν από τους μύες μελετήθηκαν για διηθήσεις και καταστροφές της λευκής ουσίας που οφείλονται στην ασθένεια ενώ μελετήθηκαν και τα επίπεδα κυτταροκινών στον ορό αίματος στα διάφορα στάδια εξέλιξης της νόσου.

scholarly journals c-Jun N-Terminal Kinase as a Therapeutic Target in Experimental Autoimmune Encephalomyelitis

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2154
Author(s):  
Maud Bagnoud ◽  
Myriam Briner ◽  
Jana Remlinger ◽  
Ivo Meli ◽  
Sara Schuetz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cell ◽  
Disease Onset ◽  
Autoimmune Encephalomyelitis ◽  
Necrosis Factor Alpha ◽  
Experimental Autoimmune

c-Jun N-terminal kinase (JNK) is upregulated during multiple sclerosis relapses and at the peak of experimental autoimmune encephalomyelitis (EAE). We aim to investigate the effects of pharmacological pan-JNK inhibition on the course of myelin oligodendrocyte glycoprotein (MOG35-55) EAE disease using in vivo and in vitro experimental models. EAE was induced in female C57BL/6JRj wild type mice using MOG35-55. SP600125 (SP), a reversible adenosine triphosphate competitive pan-JNK inhibitor, was then given orally after disease onset. Positive correlation between SP plasma and brain concentration was observed. Nine, but not three, consecutive days of SP treatment led to a significant dose-dependent decrease of mean cumulative MOG35-55 EAE severity that was associated with increased mRNA expression of interferon gamma (INF-γ) and tumor necrosis factor alpha (TNF-α) in the spinal cord. On a histological level, reduced spinal cord immune cell-infiltration predominantly of CD3+ T cells as well as increased activity of Iba1+ cells were observed in treated animals. In addition, in vitro incubation of murine and human CD3+ T cells with SP resulted in reduced T cell apoptosis and proliferation. In conclusion, our study demonstrates that pharmacological pan-JNK inhibition might be a treatment strategy for autoimmune central nervous system demyelination.

scholarly journals Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis

2005 ◽  
Vol 202 (3) ◽  
pp. 445-455 ◽  
Author(s):  
Niklas Beyersdorf ◽  
Stefanie Gaupp ◽  
Karen Balbach ◽  
Jens Schmidt ◽  
Klaus V. Toyka ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Cell Subset ◽  
High Dose ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Experimental Autoimmune

CD4+CD25+ regulatory T cells (T reg cells) play a key role in controlling autoimmunity and inflammation. Therefore, therapeutic agents that are capable of elevating numbers or increasing effector functions of this T cell subset are highly desirable. In a previous report we showed that a superagonistic monoclonal antibody specific for rat CD28 (JJ316) expands and activates T reg cells in vivo and upon short-term in vitro culture. Here we demonstrate that application of very low dosages of the CD28 superagonist into normal Lewis rats is sufficient to induce T reg cell expansion in vivo without the generalized lymphocytosis observed with high dosages of JJ316. Single i.v. administration of a low dose of the CD28 superagonist into Dark Agouti (DA) rats or Lewis rats that suffered from experimental autoimmune encephalomyelitis (EAE) proved to be highly and equally efficacious as high-dose treatment. Finally, we show that T reg cells that were isolated from CD28-treated animals displayed enhanced suppressive activity toward myelin basic protein–specific T cells in vitro, and, upon adoptive transfer, protected recipients from EAE. Our data indicate that this class of CD28-specific monoclonal antibodies targets CD4+CD25+ T reg cells and provides a novel means for the effective treatment of multiple sclerosis and other autoimmune diseases.

scholarly journals Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xiaojun Liu ◽  
Jinyun Ma ◽  
Guiqing Ding ◽  
Qianyi Gong ◽  
Yuanhua Wang ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Activated Microglia ◽  
Tnf Α ◽  
Microglia Polarization ◽  
M1 Type ◽  
M2 Phenotype ◽  
Experimental Autoimmune

Activated microglia is considered to be major mediators of the neuroinflammatory environment in demyelinating diseases of the central nervous system (CNS). Activated microglia are mainly polarized into M1 type, which plays a role in promoting inflammation and demyelinating. However, the proportion of microglia polarized into M2 type is relatively low, which cannot fully play the role of anti-inflammatory and resistance to demyelinating. Our previous study found that Astragalus polysaccharides (APS) has an immunomodulatory effect and can inhibit neuroinflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), which is a classic animal model of CNS demyelinating disease. In this study, we found that APS was effective in treating EAE mice. It restored microglia balance by inhibiting the polarization of microglia to M1-like phenotype and promoting the polarization of microglia to M2-like phenotype in vivo and in vitro. miR-155 is a key factor in regulating microglia polarization. We found that APS could inhibit the expression level of miR-155 in vivo and in vitro. Furthermore, we performed transfection overexpression and blocking experiments. The results showed that miR-155 mediated the polarization of microglia M1/M2 phenotype, while the selective inhibitor of miR-155 attenuated the inhibition of APS on microglia M1 phenotype and eliminated the promotion of APS on microglia M2 phenotype. Microglia can secrete IL-1α, TNF-α, and C1q after polarizing into M1 type and induce the activation of A1 neurotoxic astrocytes, further aggravating neuroinflammation and demyelination. APS reduced the secretion of IL-1α, TNF-α, and C1q by activated microglia, thus inhibited the formation of A1 neurotoxic astrocytes. In summary, our study suggests that APS regulates the polarization of microglia from M1 to M2 phenotype by inhibiting the miR-155, reduces the secretion of inflammatory factors, and inhibits the activation of neurotoxic astrocytes, thus effectively treating EAE.

scholarly journals Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice through inducing apoptosis of CD4+ T cells

2020 ◽  
Author(s):  
Ke An ◽  
Mengjiao Xue ◽  
Jiaying Zhong ◽  
Shengnan Yu ◽  
Zhongquan Qi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Arsenic Trioxide ◽  
Microglia Activation ◽  
Autoimmune Encephalomyelitis ◽  
Post Immunization ◽  
Experimental Autoimmune

Abstract Background: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by severe demyelination of white matter. There is no definite cure for MS owing to its complex pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for the study of MS. Arsenic trioxide (ATO) is an ancient Chinese medicine used for its therapeutic properties for several autoimmune diseases. It is also used to inhibit acute immune rejection due to its anti-inflammatory and immunosuppressive properties. However, it is unclear whether ATO has a therapeutic effect on EAE, and the underlying mechanisms have not been clearly elucidated. In this study, we attempted to explore the possibility of using ATO to ameliorate EAE in mice.Methods: ATO (0.5 mg/kg/day) was administered intraperitoneally to EAE mice 10 days post-immunization for 8 days. On day 22 post-immunization, the spinal cord, spleen, and blood were collected to analyze demyelination, inflammation, microglia activation, and proportion of CD4+ T cells. In vitro, for mechanistic studies, CD4+ T cells were sorted from the spleen of naïve C57BL/6 mice and treated with ATO and then used for apoptosis assay, JC-1 staining, transmission electron microscope, and western blotting.Results: ATO delayed the onset of EAE and alleviated the severity of EAE in mice. Treatment with ATO also attenuated demyelination, alleviated inflammation, reduced microglia activation and decreased the expression of IL-2, IFN-γ, IL-1β, IL-6, and TNF-α in EAE mice. Moreover, the number and proportion of CD4+ T cells in the spinal cord, spleen, and peripheral blood were reduced in ATO-treated EAE mice. Finally, ATO induced CD4+ T cells apoptosis through the mitochondrial pathway both in vitro and in vivo. Additionally, the administration of ATO had no adverse effect on the heart, liver, and kidney function and did not induce apoptosis in the spinal cord.Conclusions: Overall, our findings indicated that ATO plays a protective role in the initiation and progression of EAE and has the potential to be a novel drug in the treatment of MS.

scholarly journals Hormones in experimental autoimmune encephalomyelitis (EAE) animal models

2021 ◽  
Vol 12 (1) ◽  
pp. 164-189
Author(s):  
Majid Ghareghani ◽  
Amir Ghanbari ◽  
Ali Eid ◽  
Abdullah Shaito ◽  
Wael Mohamed ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Endocrine System ◽  
Laboratory Animals ◽  
Autoimmune Encephalomyelitis ◽  
Eae Model ◽  
Experimental Autoimmune

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which activated immune cells attack the CNS and cause inflammation and demyelination. While the etiology of MS is still largely unknown, the interaction between hormones and the immune system plays a role in disease progression, but the mechanisms by which this occurs are incompletely understood. Several in vitro and in vivo experimental, but also clinical studies, have addressed the possible role of the endocrine system in susceptibility and severity of autoimmune diseases. Although there are several demyelinating models, experimental autoimmune encephalomyelitis (EAE) is the oldest and most commonly used model for MS in laboratory animals which enables researchers to translate their findings from EAE into human. Evidences imply that there is great heterogeneity in the susceptibility to the induction, the method of induction, and the response to various immunological or pharmacological interventions, which led to conflicting results on the role of specific hormones in the EAE model. In this review, we address the role of endocrine system in EAE model to provide a comprehensive view and a better understanding of the interactions between the endocrine and the immune systems in various models of EAE, to open up a ground for further detailed studies in this field by considering and comparing the results and models used in previous studies.

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