{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:53:17Z","timestamp":1790232797019,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":8005,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1993,10]]},"abstract":"\n \n \n In chronic inflammation it is reported that serum iron is depleted and hepatic iron is increased because of reticuloendothelial system iron blockade. However, recent studies indicate that hepatic parenchymal cells increase the uptake of transferrin-bound iron after\n in vivo<\/jats:italic>\n stimulation with bacterial lipopolysaccharide, suggesting that endotoxemia itself or lipopolysaccharide-induced production of inflammation-related cytokines may also be responsible for this phenomenon. In this study the actions of inflammation-related cytokines on the synthesis of iron-binding proteins (transferrin and ferritin) and transferrin receptor and the uptake of transferrin-bound iron were investigated in a human hepatoblastoma cell line, HepG2, which is the most commonly used cell line for examining the regulation of hepatic protein synthesis by cytokines. The cells were exposed to interleukin-1\u03b2, interleukin-6 or tumor necrosis factor-\u03b1 separately for 24 hr. In each cytokine treatment group, the level of transferrin, which is secreted into the conditioned medium, was found to be decreased compared with that of untreated cells. On the other hand, the biosynthesis of ferritin was markedly elevated after the same treatment. This increase in ferritin by cytokine treatment was diminished when deferoxiamine was used concomitantly to deplete intracellular chelatable iron. After stimulation with interleukin-\u03b2, interleukin-6 or tumor necrosis factor-\u03b1,\n 59<\/jats:sup>\n Fe-labeled transferrin uptake into the cells was increased by 36%, 48%, or 18%, respectively, and this uptake was inhibited by the addition of excess unlabeled transferrin. A binding study with\n 125<\/jats:sup>\n I-labeled diferric transferrin revealed that the three cytokines increased the number of transferrin receptors on the cell surface by 1.15-fold to 1.35-fold. A metabolic labeling study using\n 35<\/jats:sup>\n S-methionine showed that the increase of transferrin-receptor expression was not caused by the redistribution between the cell surface and internal pool but by\n de novo<\/jats:italic>\n synthesis. These findings suggest that not only reticuloendothelial system blockade of iron release, but also enhanced liver cell uptake of transferrin-bound iron by cytokine stimulation as well as endotoxin is responsible for the hypoferremia seen during inflammation. (HEPATOLOGY 1993;18:874-880).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.1840180420","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T21:07:39Z","timestamp":1172956059000},"page":"874-880","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":84,"title":["Regulation of iron metabolism in HepG2 cells: A possible role for cytokines in the hepatic deposition of iron"],"prefix":"10.1097","volume":"18","author":[{"given":"Michiaki","family":"Hirayama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kohgo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Shintani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshi","family":"Fujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunori","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiro","family":"Nhtsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840180420-BIB1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1365-2141.1971.tb03424.x","volume":"21","author":"Cartwright","year":"1971","journal-title":"Br 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