Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis

Saksida, Tamara; Miljković, Djordje; Timotijević, Gordana; Stojanović, Ivana; Mijatović, Sanja; Fagone, Paolo; Mangano, Katia; Mammana, Santa; Farina, Claudio; Ascione, Ester; Maiello, Valentina; Nicoletti, Ferdinando; Stošić‐Grujičić, Stanislava

doi:10.1016/j.jneuroim.2013.07.001

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…Previous studies have shown that the MAPK signaling pathway is also critical for the differentiation of Th1 . These two signaling pathways play critical roles in the pathogenesis and development of MS/EAE . Our study demonstrated that 6‐GIN inhibited LPS‐stimulated activation of the NF‐κB and MAPK signaling pathways in BM‐DCs by suppressing the phosphorylation of NF‐κB p65, ERK1/2, and JNK, thereby inhibiting Th17 cell development.…”

Section: Discussionsupporting

confidence: 57%

Treatment with 6‐Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis

Han

et al. 2019

Molecular Nutrition Food Res

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Scope: Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder, with increasing incidence worldwide but unknown etiology. 6-Gingerol (6-GIN), a major dietary compound found in ginger rhizome, has immunomodulatory activity. However, its role in autoimmune diseases, as well as the underlying mechanisms, are unclear. In this study, it is evaluated if 6-GIN can effectively ameliorate the clinical disease severity of experimental autoimmune encephalomyelitis, an animal model of MS. Methods and results: Clinical scores of experimental autoimmune encephalomyelitis (EAE) mice are recorded daily. Inflammation of periphery and neuroinflammation of EAE mice are determined by flow cytometry analysis, ELISA, and histopathological analysis, and results show that 6-GIN significantly inhibits inflammatory cell infiltration from the periphery into the central nervous system and reduces neuroinflammation and demyelination. Flow cytometry analysis, ELISA, and quantitative PCR show that 6-GIN could suppress lipolysaccharide-induced dendritic cell (DC) activation and induce the tolerogenic DCs. Immunoblot analysis reveals that the phosphorylation of nuclear factor-κB and mitogen-activated protein kinase, two critical regulators of inflammatory signaling, are significantly inhibited in 6-GIN-treated DCs. Conclusion: The results of this study demonstrate that 6-GIN has significant potential as a novel anti-inflammatory agent for the treatment of autoimmune diseases such as MS via direct modulatory effects on DCs.

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Section: Discussionsupporting

confidence: 57%

Treatment with 6‐Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis

Han

et al. 2019

Molecular Nutrition Food Res

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“…IL-2 is known for differentiation of T cells, and is typically pro-inflammatory, as shown by Saskida, et al, suggesting this cytokine should increase as did IFN-γ 31 . But, no change was seen in these cytokines, as we have shown in literature 3,28 .…”

Section: Discussionmentioning

confidence: 93%

Pulmonary Administration of Soluble Antigen Arrays Is Superior to Antigen in Treatment of Experimental Autoimmune Encephalomyelitis

Kuehl

Thati

Sullivan

et al. 2017

Journal of Pharmaceutical Sciences

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Antigen-specific immunotherapy (ASIT) has been used to hyposensitize patients to allergens and offers an enticing approach for attenuating autoimmune diseases. Applying ASIT to mucosal surfaces such as the lungs may engage unique immune response pathways to improve efficacy. Pulmonary delivery of soluble antigen arrays (SAgAs) was explored in mice with experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. SAgAs were designed to impede immune response to autoantigen epitopes and are composed of a hyaluronan backbone with peptides PLP139–151 and LABL, a disease-causing proteolipid peptide epitope and an ICAM-1 ligand, respectively. Pulmonary instillation of SAgAs decreased disease score, improved weight gain, and decreased incidence of disease in EAE mice compared to pulmonary delivery of HA polymer, LABL, or PLP. Interestingly, treating with PLP alone also showed some improvement. Splenocytes from SAgA-treated animals showed increased IFN-γ levels, and IL-6 and IL-17 were elevated in SAgA-treated animals compared to PLP treatments. IL-10, IL-2, and TNF-α levels showed no significant difference, yet trends across all cytokines suggested SAgAs induced a very different immune response compared to treatment with PLP alone. This work suggests that co-delivery of peptide components is essential when treating EAE via pulmonary instillation, and the immune response may have shifted towards immune tolerance. a

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“…Increased levels of NF-κB in many tissues have been observed in patients with diabetes [45, 46]. Transferrin effectively suppressed intracellular signaling essential for IL-2 gene expression via inhibition of NF-κB activities [47]. Our group found that through NF-κB inhibition, P .…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic activities of polysaccharides separated from Inonotus obliquus via the modulation of oxidative stress in mice with streptozotocin-induced diabetes

Wang

et al. 2017

PLoS ONE

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This study evaluated the effects of Inonotus obliquus polysaccharides (IOs) on diabetes and other underlying mechanisms related to inflammatory factors and oxidative stress in a mouse model of streptozotocin (STZ)-induced diabetes. Four weeks administration of metformin (120 mg/kg) and IO1-4 (50%-80% alcohol precipitation), or IO5 (total 80% alcohol precipitation) at doses of 50 mg/kg reverses the abnormal changes of bodyweights and fasting blood glucose levels of diabetic mice. IOs significantly increased the insulin and pyruvate kinase levels in serum, and improved the synthesis of glycogen, especially for IO5. IOs restored the disturbed serum levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde. The down-regulation of interleukin-2 receptor, matrix metalloproteinase-9, and the enhancement of interleukin-2 in serum of diabetic mice were significantly attenuated by IOs. Histologic and morphology examinations showed that IOs repaired the damage on kidney tissues, inhibited inflammatory infiltrate and extracellular matrix deposit injuries in diabetic mice. Compared with untreated diabetic mice, IOs decreased the expression of phosphor-NF-κB in the kidneys. These results show that IOs treatment attenuated diabetic and renal injure in STZ-induced diabetic mice, possibly through the modulation of oxidative stress and inflammatory factors. These results provide valuable evidences to support the use of I. obliquus as a hypoglycemic functional food and/or medicine.

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Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis

Cited by 8 publications

References 36 publications

Treatment with 6‐Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis

Treatment with 6‐Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis

Pulmonary Administration of Soluble Antigen Arrays Is Superior to Antigen in Treatment of Experimental Autoimmune Encephalomyelitis

Antidiabetic activities of polysaccharides separated from Inonotus obliquus via the modulation of oxidative stress in mice with streptozotocin-induced diabetes

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