β-Carotene can reverse dysregulation of iron protein in an in vitro model of inflammation.
Anemia of chronic disease is frequently seen in chronic inflammatory conditions. Its hallmark is disrupted iron homeostasis, with increased uptake and retention of iron in cells of the reticuloendothelial system. Using the Caco-2 cell line as an in vitro model for iron absorption, local intestinal iron-related protein dynamics were evaluated during interleukin (IL)1β/iron-induced inflammation, confirmed by IL8 release, and following β-carotene and vitamin A supplementation. Time- and dose-dependent iron administration to the cells was then studied. The effects on heavy and light ferritin, ferroportin, transferrin receptor and intracellular iron levels were compared in inflamed Caco-2 cells with and without application of the anti-inflammatory agents β-carotene and vitamin A. IL1β treatment led to IL8 release, a surge in both ferritins' expressions and suppression of ferroportin and transferrin receptor expression. β-Carotene significantly reduced IL8 (1,306.2-253.75 pg/ml), decreased light and heavy ferritin by 77.8 and 45.8%, respectively, and increased ferroportin by 59.9% (P < 0.05). Increasing iron concentrations and incubation periods resulted in increased IL8 release. A strong correlation was found between the levels of IL8 and the ferritins. Intracellular iron sequestration was induced by IL1β and iron and alleviated by β-carotene. β-Carotene normalized the main iron-related proteins' levels, reduced IL8 production, and released intracellular trapped iron. These results highlight local mucosal control of iron regulation and suggest that by applying anti-inflammatory compounds, less iron is locked in inflamed intestinal epithelial cells, leading to its increased bioavailability. This suggests a possible approach to combating anemia associated with chronic inflammatory conditions.
The Faculty of Agriculture, Food and Environmental Sciences, The School of Nutritional Sciences, The Hebrew University of Jerusalem, 76100, Rehovot, Israel.
Oksana
O
Katz
Ram
R
Reifen
Aaron
A
Lerner
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018938:Caco-2 Cells; D002338:Carotenoids / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D042541:Intracellular Space / Q000378:metabolism; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011990:Receptors, Transferrin / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism* / Q000494:pharmacology; D000098742:Ferroportin
D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D053583:Interleukin-1beta; D016209:Interleukin-8; D011990:Receptors, Transferrin; D000098742:Ferroportin; D019207:beta Carotene; D002338:Carotenoids; D005293:Ferritins; D007501:Iron