Dihydroartemisinin ameliorates murine experimental autoimmune encephalomyelitis through enhancing co-inhibitory signals

2020 ◽  
Vol 10 (11) ◽  
pp. 1824-1830
Author(s):  
Qingsen Ran ◽  
Qi Li ◽  
Li Liu ◽  
Lidong Sun ◽  
Qing Yang ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Immunological Response ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Cytotoxic Lymphocyte ◽  
Autoimmune Encephalomyelitis ◽  
Protein Levels ◽  
Programmed Cell Death 1 ◽  
Physical Functions ◽  
Experimental Autoimmune

Dihydroartemisinin (DHA) has shown a significant effect in anti-inflammation. This study is aimed at detecting the effect of DHA in Experimental Autoimmune Encephalomyelitis (EAE), which is characterized by neuroinflammation and demyelination using Myelin Oligodendrocyte Glycoprotein (MOG35-55) to induce EAE model in female C57BL/6 mice. The physical functions and histopathological structures were analyzed during the acute phase. Furthermore, flow cytometry was used to test the functionality of the immunological response in splenocytes. Western blot and qRT-PCR assays were used to investigate protein levels and gene expression, respectively. Pharmacologically, mice treated with DHA had smaller spinal cord lesions with fewer inflammatory cuffs than those EAE mice had. Mechanically, DHA enhanced the expression of both Cytotoxic Lymphocyte Antigen 4 (CTLA4) and Programmed cell Death 1 (PD1) in splenocytes. Moreover, DHA up-regulated the expression of Suppressor of Cytokine Signaling 3 (SOCS3) and the phosphorylation of Signal Transduction and Activator of Transcription 1 (STAT1). In conclusion, DHA can ameliorate EAE and up-regulate the expression of CTLA4 and PD1 on T cells via STAT1/SOCS3 pathway, indicating that DHA has huge potential for development as a therapeutic agent for MS.

scholarly journals Modulation of Neurological Deficits and Expression of Glutamate Receptors during Experimental Autoimmune Encephalomyelitis after Treatment with Selected Antagonists of Glutamate Receptors

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Grzegorz Sulkowski ◽  
Beata Dąbrowska-Bouta ◽  
Lidia Strużyńska
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Protein Expression ◽  
Mrna Expression ◽  
Glutamate Receptors ◽  
Neurological Deficits ◽  
Autoimmune Encephalomyelitis ◽  
Protein Levels ◽  
Group I ◽  
Group I Mglurs ◽  
Experimental Autoimmune

The aim of our investigation was to characterize the role of group I mGluRs and NMDA receptors in pathomechanisms of experimental autoimmune encephalomyelitis (EAE), the rodent model of MS. We tested the effects of LY 367385 (S-2-methyl-4-carboxyphenylglycine, a competitive antagonist of mGluR1), MPEP (2-methyl-6-(phenylethynyl)-pyridine, an antagonist of mGluR5), and the uncompetitive NMDA receptor antagonists amantadine and memantine on modulation of neurological deficits observed in rats with EAE. The neurological symptoms of EAE started at 10-11 days post-injection (d.p.i.) and peaked after 12-13 d.p.i. The protein levels of mGluRs and NMDA did not increase in early phases of EAE (4 d.p.i.), but starting from 8 d.p.i. to 25 d.p.i., we observed a significant elevation of mGluR1 and mGluR5 protein expression by about 20% and NMDA protein expression by about 10% over the control at 25 d.p.i. The changes in protein levels were accompanied by changes in mRNA expression of group I mGluRs and NMDARs. During the late disease phase (20–25 d.p.i.), the mRNA expression levels reached 300% of control values. In contrast, treatment with individual receptor antagonists resulted in a reduction of mRNA levels relative to untreated animals.

scholarly journals Role of SOCS2 in the Regulation of Immune Response and Development of the Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Allysson Cramer ◽  
Bruno Cabral de Lima Oliveira ◽  
Paulo Gaio Leite ◽  
David Henrique Rodrigues ◽  
Fatima Brant ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Immune Response ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Acute Phase ◽  
Critical Role ◽  
Recovery Phase ◽  
Cytokine Signaling ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Experimental Autoimmune Encephalomyelitis (EAE) is the most widely used animal model for the study of MS. The Suppressor of Cytokine Signaling (SOCS) 2 protein plays a critical role in regulating the immune responses. The role of SOCS2 during EAE has not been explored. EAE was induced in WT and SOCS2-/- mice using myelin oligodendrocyte glycoprotein (MOG35-55) peptide. Brain and spinal cord were examined during the peak (day 14) and recovery phase (day 28) of the disease. SOCS2 was upregulated in the brain of WT mice at the peak and recovery phase of EAE. The development of the acute phase was slower in onset in SOCS2-/- mice and was associated with reduced number of Th1 (CD3+CD4+IFN-γ+) cells in the spinal cord and brain. However, while in WT mice, maximal clinical EAE score was followed by a progressive recovery; the SOCS2-/- mice were unable to recover from locomotor impairment that occurred during the acute phase. There was a prolonged inflammatory response (increased Th1 and decreased Th2 and T regulatory cells) in the late phase of EAE in the CNS of SOCS2-/- mice. Transplantation of bone marrow cells from SOCS2-/- into irradiated WT mice resulted in higher lethality at the early phase of EAE. Altogether, these results suggest that SOCS2 plays a dual role in the immune response during EAE. It is necessary for damage during the acute phase damage but plays a beneficial role in the recovery stage of the disease.

Sign in / Sign up

Export Citation Format

Share Document