• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.525-529
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• 2003

The phosphorylation of extracellular signal-regulated kinases (p-ERK) in the spinal cord of rats with acute monophasic experimental autoimmune encephalomyelitis (EAE) was studied using immunohistochemistry and treatment with inhibitor. P-ERK is constitutively expressed in glial cells in the normal spinal cord. In EAE, some inflammatory cells in the subarachnoid space were positive for p-ERK at the early stage, and its immunoreactivity declined when those cells infiltrated the parenchyma at the peak stage. In a blocking experiment using its inhibitor, the intravenous administration of PD98059 from day 7 to 13 post-immunization did not modulate EAE paralysis. Considering the results, we postulate that intravenous administration of PD98059 is not effective in ameliorating EAE paralysis, although many inflammatory cells express ERK in the subarachnoid space.

• Korean Journal of Veterinary Research
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• v.44 no.3
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• pp.349-355
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• 2004

The aim of this study was to evaluate the expression of galectin-3, one of beta-galactoside-binding proteins, in the experimental autoimmune encephalomyelitis(EAE) model of Lewis rats or non-obese diabetic (NOD) mice. Western blot analysis showed that galectin-3 was weakly expressed in the spinal cords of complete Freund's adjuvant(CFA) immunized control rats. In EAE, however, galectin-3 expression was significantly increased at the peak stage(days 14 post-immunization), while it was decreased slightly at the recovery stage(day 21 post-immunization). Immunohistochemical analysis showed that galectin-3 was detected in some macrophages in demyelinating lesions of NOD mice, while galectin-3 was immunoreacted in some inflammatory cells in the perivascular cuffing in rat EAE lesions. Collectively, it is postulated that the expression of galectin-3 is significantly increased in response to neuroimmunological stimulation in the central nervous system, whereas it is weak in normal rats and mice.

• Journal of Veterinary Science
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• v.25 no.3
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• pp.35.1-35.13
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• 2024

Importance: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. Objective: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. Methods: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein_35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. Results: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. Conclusions and Relevance: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

• Korean Journal of Veterinary Pathology
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• v.2 no.1
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• pp.31-36
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• 1998

The Opuntia ficus-indica extract(OFE) has been claimed to have several therapeutic properties including anti-inflammation and anti-rheumatoid arthritis in oriental medicine but little is known about their effect on macrophages. This study demonstrated that OFE could stimulate TNF-alpha production in cultured macrophages. which is one of important mediators in autoimmune diseases including experimental autoimmune encephalomyelitis(EAE). In vivo study showed that oral administration of OFE exacerbate the onset of clinical paralysis. This finding suggests that OFE stimulates cytokine production and exacerbates autoimmune inflammatory diseases including EAE.

• Korean Journal of Veterinary Research
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• v.54 no.4
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• pp.209-218
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• 2014

Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), reflects pathophysiologic steps in MS such as the influence of T cells and antibodies reactive to the myelin sheath, and the cytotoxic effect of cytokines. Galectin-9 (Gal-9) is a member of animal lectins that plays an essential role in various biological functions. The expression of Gal-9 is significantly enhanced in MS lesions; however, its role in autoimmune disease has not been fully elucidated. To identify the role of Gal-9 in EAE, we measured changes in mRNA and protein expression of Gal-9 as EAE progressed. Expression increased with disease progression, with a sharp rise occurring at its peak. Gal-9 immunoreactivity was mainly expressed in astrocytes and microglia of the central nervous system (CNS) and macrophages of spleen. Flow cytometric analysis revealed that $Gal-9^+CD11b^+$ cells were dramatically increased in the spleen at the peak of disease. Increased expression of tumor necrosis factor (TNF)-R1 and p-Jun N-terminal kinase (JNK) was observed in the CNS of EAE mice, suggesting that TNF-R1 and p-JNK might be key regulators contributing to the expression of Gal-9 during EAE. These results suggest that identification of the relationship between Gal-9 and EAE progression is critical for better understanding Gal-9 biology in autoimmune disease.

• Korean Journal of Veterinary Research
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• v.46 no.3
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• pp.177-184
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• 2006

Experimental autoimmune encephalomyelitis (EAE) is a disease model of multiple sclerosis (MS) that is characterized by remittance and relapse of the disease and autoimmune and demyelinating lesions in the central nervous system (CNS). Autoimmune inflammation is maintained by secretion of a large number of protein. Previous studies have suggested that transcripts encoding osteopontin (OPN) are frequently detected in the mRNA population of MS plaques. To elucidate the functional role of OPN in initiation and development of EAE, we examined the expression and localization of OPN in the spinal cord during acute EAE. We demonstrated that OPN significantly increased at the early stage of EAE and slightly declined thereafter by western blot analysis. An immunohistochemical study revealed that OPN was constitutively expressed in some glial cells (microglia, astrocytes) of white matter and neurons in the CNS of control rats. OPN expression was shown to be increased in the same cells at the early and peak stage of EAE. To identity cells expressing OPN by double-immunofluorescence labeling, we labeled rat spinal cord sections for OPN with a monoclonal OPN antibody and with mAbs for astrocyte (GFAP), microglia/macrophage (OX42)-specific markers. The major cell types of OPN-expressing cells were activated astrocytes and microglia in the adjacent inflammatory lesions. Interestingly, OPN was mainly expressed in the end feet of astrocytes around vascular cell adhesion molecule-1 (VCAM-1) expressing endothelial cells of CNS blood vessel. These findings suggest that increased levels of OPN in activated glial cell may play an important role in the recruitment of inflammatory cells into the CNS parenchyma during EAE.

• Annals of Clinical Neurophysiology
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• v.7 no.1
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• pp.37-42
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• 2005

Acute disseminated encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (Hurst's disease) are rare autoimmune demyelinating disorders, which show a monophasic illness with preceding infection. We report a 42-year-old woman presented with multiphasic and progressive neurologic deterioration without definite evidences of infection. She developed hypesthetic ataxia, followed by ipsilateral weakness after a weak, and finally encephalopathy after a month. In contrast to the first MRI showing a small longitudinal lesion, the next images revealed massive bilateral frontal lesions with hemorrhagic necrosis and biopsy unveiled inflammatory demyelination.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.81-88
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• 2014

Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-${\beta}$, hepatic growth factors, prostaglandin $E_2$, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.18.1-18.13
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• 2021

TLR signaling is critical for broad scale immune recognition of pathogens and/or danger molecules. TLRs are particularly important for the activation and the maturation of cells comprising the innate immune response. In recent years it has become apparent that several different TLRs regulate the function of lymphocytes as well, albeit to a lesser degree compared to innate immunity. TLR2 heterodimerizes with either TLR1 or TLR6 to broadly recognize bacterial lipopeptides as well as several danger-associated molecular patterns. In general, TLR2 signaling promotes immune cell activation leading to tissue inflammation, which is advantageous for combating an infection. Conversely, inappropriate or dysfunctional TLR2 signaling leading to an overactive inflammatory response could be detrimental during sterile inflammation and autoimmune disease. This review will highlight and discuss recent research advances linking TLR2 engagement to autoimmune inflammation.

• Korean Journal of Veterinary Research
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• v.51 no.3
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• pp.217-225
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• 2011

Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B ($NF{\kappa}B$) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, $NF{\kappa}B$ activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of $NF{\kappa}B$ activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of $NF{\kappa}B$ and phospho-$I{\kappa}B$ proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of $NF{\kappa}B$ and phospho-$I{\kappa}B$ significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of $NF{\kappa}B$ and phophorylation of $I{\kappa}B$ in the CNS. Subsequently, the inhibition of $NF{\kappa}B$ activation and $I{\kappa}B$ phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.