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Anti-inflammatory properties of a novel peptide interleukin 1 receptor antagonist.


ABSTRACT: 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-1?-induced activation of nuclear factor ?B (NF-?B) in HEK-Blue cells that contained an IL-1?-sensitive reporter, the secretion of TNF-? 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-1?-induced activation of NF-?B, and inhibited the secretion of TNF-? 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.

SUBMITTER: Klementiev B 

PROVIDER: S-EPMC3923439 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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<h4>Background</h4>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.<h4>Methods</h4>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  ...[more]

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