Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation

2012 ◽  
Vol 51 (2) ◽  
pp. 210-218 ◽  
Author(s):  
Loes M. Kuijk ◽  
Elsenoor J. Klaver ◽  
Gijs Kooij ◽  
Susanne M.A. van der Pol ◽  
Priscilla Heijnen ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Cell Activation ◽  
Clinical Signs ◽  
Human Dendritic Cell ◽  
Dendritic Cell Activation ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Silybin Alleviates Experimental Autoimmune Encephalomyelitis by Suppressing Dendritic Cell Activation and Th17 Cell Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan-Li Yang ◽  
Xiao-Wu Shi
Keyword(s):  
Cell Differentiation ◽  
Dendritic Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cell ◽  
Cell Activation ◽  
Flavonoid Compound ◽  
Dendritic Cell Activation ◽  
Autoimmune Encephalomyelitis ◽  
Th17 Cell Differentiation ◽  
Experimental Autoimmune

Silybin, a peculiar flavonoid compound derived from the fruit and seeds of Silybum marianum, exhibits strong anti-inflammatory activities. In the present study, we found that silybin effectively alleviated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), via inhibition of dendritic cell (DC) activation and Th17 cell differentiation. Silybin treatment greatly ameliorated the disease severity and significantly declined inflammation and demyelination of the central nervous system (CNS) of EAE mice. Consistent with the disease development, silybin-treated bone marrow-derived DCs (BM-DCs) exhibited reduced costimulatory molecules (e.g., CD80 and CD86) and MHC II expression. These results demonstrated the distinguished bioactivity of silybin for suppressing DC activation, inhibiting pathogenic Th17 inflammatory cell responses, and, eventually, alleviating EAE severity. Taken together, our results show that silybin has high potential for the development of a novel therapeutic agent for the treatment of autoimmune diseases such as MS.

scholarly journals The induced dose of experimental autoimmune encephalomyelitis was not determinant and proportional to histopathological findings

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Maiara Carolina Perussolo ◽  
Bassam Felipe Mogharbel ◽  
Lucia de Noronha ◽  
Katherine Athayde Teixeira de Carvalho
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Histopathological Findings ◽  
The Brain ◽  
Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized as an inflammatory demyelinating disease. It presents a diversity of neurologic signs and symptoms as well the incapacities. Since the need for advances in MS treatment, many studies are for new therapeutic technologies, mainly through using preclinical models as experimental autoimmune encephalomyelitis (EAE). This study aimed to observe and analyze the development in Lewis rats-induced model of EAE. Methods It was used 23 females of Rattus norvegicus, from 6 to 8 weeks, weighing around 170 g. Of 23 rats, 19 underwent EAE induction distributed in six groups to establish the evolution of clinical signs. B. pertussis toxin (PTX) doses were 200, 250, 300, 350–400 ng, and four animals as the control group. The animals had weight and scores analyzed daily, starting seven and ending 24 days after induction. Then, all animals were euthanized, and the brain and spinal cord were collected for histopathological analyses. Results The results showed that the dose of 250 ng of PTX induced de higher score and weight reduction. All groups who received the PTX demonstrated histopathological findings. Those characterized as leukocyte infiltration, activation of microglia and astrocytes, and demyelinated plaques in the brain. In the spinal cord, the loosening of the myelinated fibers was observed by increasing the axonal space in all tested doses of PTX. Conclusions EAE was not dose-dependent. Histopathological findings do not proportionally related to clinical signs, as in human patients with MS.

scholarly journals Inhalation of Dimethyl Fumarate-encapsulated solid lipid nanoparticles attenuate clinical signs of Experimental Autoimmune Encephalomyelitis and pulmonary inflammatory dysfunction in mice

2021 ◽  
Author(s):  
Bárbara Fernandes Pinto ◽  
Lorena Natasha Brito Ribeiro ◽  
Gisela Bevilacqua Rolfsen Ferreira da Silva ◽  
Camila Simões Freitas ◽  
Lucas Kraemer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Solid Lipid Nanoparticles ◽  
Clinical Signs ◽  
Dimethyl Fumarate ◽  
Lipid Nanoparticles ◽  
Oral Drug ◽  
Autoimmune Encephalomyelitis ◽  
Solid Lipid ◽  
Experimental Autoimmune

Rationale: The FDA approved Dimethyl Fumarate (DMF) as an oral drug for Multiple Sclerosis treatment based on its immunomodulatory activities. However, it also caused severe adverse effects mainly related to the gastrointestinal system. Objective: Investigated the potential effects of solid lipid nanoparticles (SLN) containing DMF, administered by inhalation on the clinical signs, central nervous system (CNS) inflammatory response, and lung function changes in mice with experimental autoimmune encephalomyelitis (EAE). Materials and Methods: EAE was induced using MOG35-55 peptide in female C57BL/6J mice and were treated via inhalation with DMF-encapsulated SLN (CTRL/SLN/DMF and EAE/SLN/DMF), empty SLN (CTRL/SLN and EAE/SLN), or saline solution (CTRL/saline and EAE/saline), every 72 hours during 21 days. Results: After 21 days post-induction, EAE mice treated with DMF-loaded SLN, when compared to EAE/saline and EAE/SLN, showed decreased clinical score and weight loss, reduction in brain and spinal cord injury and inflammation, also related to the increased influx of Foxp3+ cells into the spinal cord and lung tissues. Moreover, our data revealed that EAE mice showed signs of respiratory disease, marked by increased vascular permeability, leukocyte influx, production of TNF-α and IL-17, perivascular and peribronchial inflammation, with pulmonary mechanical dysfunction associated with loss of respiratory volumes and elasticity, which DMF-encapsulated reverted in SLN nebulization. Conclusion: Our study suggests that inhalation of DMF-encapsulated SLN is an effective therapeutic protocol that reduces not only the CNS inflammatory process and disability progression, characteristic of EAE disease, but also protects mice from lung inflammation and pulmonary dysfunction.

scholarly journals Interleukin-19 Abrogates Experimental Autoimmune Encephalomyelitis by Attenuating Antigen-Presenting Cell Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hiroshi Horiuchi ◽  
Bijay Parajuli ◽  
Hiroyasu Komiya ◽  
Yuki Ogawa ◽  
Shijie Jin ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Mhc Class Ii ◽  
Th17 Cell ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Autoimmune Encephalomyelitis ◽  
Therapeutic Benefits ◽  
Ms Pathogenesis ◽  
Experimental Autoimmune

Interleukin-19 (IL-19) acts as a negative-feedback regulator to limit proinflammatory response of macrophages and microglia in autocrine/paracrine manners in various inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system (CNS), but it remains uncertain how IL-19 contributes to MS pathogenesis. Here, we demonstrate that IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by promoting IL-17-producing helper T cell (Th17 cell) infiltration into the CNS. In addition, IL-19-deficient splenic macrophages expressed elevated levels of major histocompatibility complex (MHC) class II, co-stimulatory molecules, and Th17 cell differentiation-associated cytokines such as IL-1β, IL-6, IL-23, TGF-β1, and TNF-α. These observations indicated that IL-19 plays a critical role in suppression of MS pathogenesis by inhibiting macrophage antigen presentation, Th17 cell expansion, and subsequent inflammatory responses. Furthermore, treatment with IL-19 significantly abrogated EAE. Our data suggest that IL-19 could provide significant therapeutic benefits in patients with MS.

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