title: Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection.
abstract: The proinflammatory cytokine interleukin-1beta (IL-1beta) contributes to inflammation and neuronal death in CNS injuries and neurodegenerative pathologies, and astrocytes have been implicated as the primary mediators of IL-1beta induced neuronal death. As astrocytes play an important role in supporting the survival and functions of neurons, we investigated the effect of plant flavonoids quercetin and luteolin, with known anti-inflammatory properties in modulating the response of human astrocytes to IL-1beta for therapeutic intervention. Flavonoids significantly decreased the release of reactive oxygen species (ROS) from astrocytes stimulated with IL-1beta. This decrease was accompanied by an increase in expression of superoxide dismutase (SOD-1) and thioredoxin (TRX1)-mediators associated with protection against oxidative stress. Flavonoids not only modulated the expression of astrocytes specific molecules such as glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and ceruloplasmin (CP) both in the presence and absence of IL-1beta but also decreased the elevated levels of proinflammatory cytokine interleukin-6 (IL-6) and chemokines interleukin-8 (IL-8), interferon-inducible protein (IP-10), monocyte-chemoattractant protein-1 (MCP-1), and RANTES from IL-1beta activated astrocytes. Significant decrease in neuronal apoptosis was observed in neurons cultured in conditioned medium obtained from astrocytes treated with a combination of IL-1beta and flavonoids as compared to that treated with IL-1beta alone. Our result suggests that by (i) enhancing the potential of activated astrocytes to detoxify free radical, (ii) reducing the expression of proinflammatory cytokines and chemokines, and (iii) modulating expression of mediators associated with enhanced physiological activity of astrocyte in response to injury, flavonoids confer (iv) protection against IL-1beta induced astrocyte mediated neuronal damage.
authors.affiliation: National Brain Research Centre, Manesar, Haryana 122 050, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Sharma
authors.forename: Mamata
authors.initials: M
authors.lastname: Mishra
authors.forename: Soumya
authors.initials: S
authors.lastname: Ghosh
authors.forename: Richa
authors.initials: R
authors.lastname: Tewari
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.forename: Ellora
authors.initials: E
authors.lastname: Sen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005333:Fetus / Q000166:cytology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology*; D047311:Luteolin / Q000494:pharmacology; D018696:Neuroprotective Agents; D011794:Quercetin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D011794:Quercetin; D047311:Luteolin