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

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

Calcium and cyclic nucleotides affect TNF-alpha-induced stem cell migration.

Contains fulltext : 80403.pdf (publisher's version ) (Closed access)The purpose of this study was to study the effect of calcium, cyclic AMP (cAMP) and cyclic GMP (cGMP) on embryonic stem cell (ESC) motility during TNF-alpha-induced chemotaxis. ESCs were monitored using a chemotaxis chamber, with different concentrations of calcium or cAMP or cGMP added to the medium. Changes in intracellular calcium ([Ca(2+)](i)) were measured with the fluorescent dye fura-2/AM. We combined migratory parameters in a mathematical model and described it as "mobility". After adding calcium, a dose-dependant increase in cell speed was found. Cyclic AMP increased mobility as well as the [Ca(2+)](i). In contrast, adding dbcGMP resulted in a significant decrease in the mobility of the ESCs. During migration ESCs showed an increase in [Ca(2+)](i). Furthermore, TNF-alpha dramatically increased the movement as well as the directionality of ESCs. These results demonstrate that ESCs are highly motile and respond to different concentrations of calcium in a dose-related manner