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

TY - JOUR

T1 - Anti-inflammatory properties of a novel peptide interleukin 1 receptor antagonist

AU - Klementiev, Boris

AU - Li, Shizhong

AU - Korshunova, Irina

AU - Dmytriyeva, Oksana

AU - Pankratova, Stanislava

AU - Walmod, Peter S

AU - Kjær, Laura K

AU - Dahllöf, Mattias S

AU - Lundh, Morten

AU - Christensen, Dan P

AU - Mandrup-Poulsen, Thomas

AU - Bock, Elisabeth

AU - Berezin, Vladimir

PY - 2014/2/3

Y1 - 2014/2/3

N2 - 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.

AB - 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.

U2 - 10.1186/1742-2094-11-27

DO - 10.1186/1742-2094-11-27

M3 - Journal article

C2 - 24490798

SN - 1742-2094

VL - 11

SP - 27

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

IS - 1

ER -