University of Ioannina

About: University of Ioannina is a education organization based out in Ioannina, Greece. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 7654 authors who have published 20594 publications receiving 671560 citations. The organization is also known as: Panepistimio Ioanninon.

Luteolin Inhibits an Endotoxin-Stimulated Phosphorylation Cascade and Proinflammatory Cytokine Production in Macrophages

Abstract: Flavonoids are naturally occurring polyphenolic compounds with a wide distribution throughout the plant kingdom. In the present study, we compared the ability of several flavonoids to modulate the production of proinflammatory molecules from lipopolysaccharide (LPS)-stimulated macrophages and investigated their mechanism(s) of action. Pretreatment of RAW 264.7 with luteolin, luteolin-7-glucoside, quercetin, and the isoflavonoid genistein inhibited both the LPS-stimulated TNF-alpha and interleukin-6 release, whereas eriodictyol and hesperetin only inhibited TNF-alpha release. From the compounds tested luteolin and quercetin were the most potent in inhibiting cytokine production with an IC(50) of less than 1 and 5 microM for TNF-alpha release, respectively. To determine the mechanisms by which flavonoids inhibit LPS signaling, we used luteolin and determined its ability to interfere with total protein tyrosine phosphorylation as well as Akt phosphorylation and nuclear factor-kappaB activation. Pretreatment of the cells with luteolin attenuated LPS-induced tyrosine phosphorylation of many discrete proteins. Moreover, luteolin inhibited LPS-induced phosphorylation of Akt. Treatment of macrophages with LPS resulted in increased IkappaB-alpha phosphorylation and reduced the levels of IkappaB-alpha. Pretreatment of cells with luteolin abolished the effects of LPS on IkappaB-alpha. To determine the functional relevance of the phosphorylation events observed with IkappaB-alpha, macrophages were transfected either with a control vector or a vector coding for the luciferase reporter gene under the control of kappaB cis-acting elements. Incubation of transfected RAW 264.7 cells with LPS increased luciferase activity in a luteolin-sensitive manner. We conclude that luteolin inhibits protein tyrosine phosphorylation, nuclear factor-kappaB-mediated gene expression and proinflammatory cytokine production in murine macrophages.

Oxidative stress and iron homeostasis: mechanistic and health aspects.

Abstract: Iron is an essential cofactor for important biological activities and biochemical reactions, including the transport of oxygen via red blood cells and its reduction to water during respiration. While iron's bioavailability is generally limited, pathological accumulation of the metal within tissues aggravates the generation of reactive oxygen species (ROS) and elicits toxic effects, which are mainly related to oxidative stress. Here, we describe the role of iron in ROS-induced toxicity and discuss molecular mechanisms and physiological aspects of ROS- and iron-mediated signaling. In addition, we review our current understanding of the regulation of iron homeostasis at the cellular and systemic levels, and focus on the pathogenesis and management of iron overload disorders.