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Anti-inflammatory properties of a novel peptide interleukin 1 receptor antagonist
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نویسنده
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klementiev b. ,li s. ,korshunova i. ,dmytriyeva o. ,pankratova s. ,walmod p.s. ,kjær l.k. ,dahllöf m.s. ,lundh m. ,christensen d.p. ,mandrup-poulsen t. ,bock e. ,berezin v.
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منبع
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journal of neuroinflammation - 2014 - دوره : 11 - شماره : 0
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چکیده
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Background: interleukin 1 (il-1) is implicated in neuroinflammation,an essential component of neurodegeneration. we evaluated the potential anti-inflammatory effect of a novel peptide antagonist of il-1 signaling,ilantide.methods: we investigated the binding of ilantide to il-1 receptor type i (il-1ri) using surface plasmon resonance,the inhibition of il-1β-induced activation of nuclear factor κb (nf-κb) in hek-blue cells that contained an il-1β-sensitive reporter,the secretion of tnf-α in macrophages,protection against il-1-induced apoptosis in neonatal pancreatic islets,and the penetration of ilantide through the blood-brain barrier using competitive enzyme-linked immunosorbent assay (elisa). we studied the effects of the peptide on social behavior and memory in rat models of lipopolysaccharide (lps)- and amyloid-induced neuroinflammation,respectively,and its effect in a rat model of experimental autoimmune enchephalomyelitis.results: ilantide bound il-1ri,inhibited the il-1β-induced activation of nf-κb,and inhibited the secretion of tnf-α in vitro. ilantide protected pancreatic islets from apoptosis in vitro and reduced inflammation in an animal model of arthritis. the peptide penetrated the blood-brain barrier. it reduced the deficits in social activity and memory in lps- and amyloid-treated animals and delayed the development of experimental autoimmune enchephalomyelitis.conclusions: these findings indicate that ilantide is a novel and potent il-1ri antagonist that is able to reduce inflammatory damage in the central nervous system and pancreatic islets. © 2014 klementiev et al.; licensee biomed central ltd.
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کلیدواژه
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Amyloid-β; Antagonistic peptide; Experimental autoimmune encephalitis; Inflammation; Interleukin 1; LPS; Pancreatic islets
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آدرس
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laboratory of neural plasticity,department of neuroscience and pharmacology,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, laboratory of neural plasticity,department of neuroscience and pharmacology,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, laboratory of neural plasticity,department of neuroscience and pharmacology,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, laboratory of neural plasticity,department of neuroscience and pharmacology,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, laboratory of neural plasticity,department of neuroscience and pharmacology,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, laboratory of neural plasticity,department of neuroscience and pharmacology,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, section of endocrinological research,department of biomedical sciences,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, section of endocrinological research,department of biomedical sciences,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, section of endocrinological research,department of biomedical sciences,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, section of endocrinological research,department of biomedical sciences,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, section of endocrinological research,department of biomedical sciences,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen,denmark,department of molecular medicine and surgery,karolinska institute,solna (l1:00),se-171 77 stockholm, Sweden, laboratory of neural plasticity,department of neuroscience and pharmacology,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark, laboratory of neural plasticity,department of neuroscience and pharmacology,university of copenhagen,blegdamsvej 3,dk-2200 copenhagen, Denmark
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Authors
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