Cytokine-mediated regulation of transferrin synthesis in mouse macrophages and human T lymphocytes

Abstract

Transferrin (Tf) plays an important role during immunologic activation by donating iron to activated lymphocytes. Therefore, synthesis by lymphomyeloid cells has been investigated. Mouse macrophages and macrophage cell lines synthesized Tf, with levels being markedly increased by gamma-interferon (gamma-IFN) and, to a lesser extent, by interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF alpha). Tf was also produced by phytohemagglutinin-stimulated human T cells and two T-cell lines and was increased by IL-2. Even after appropriate activation, none was synthesized by human macrophages or monocytic cell lines or by mouse T cells, T-cell lines, or thymus cells. In both species, B-lineage cell lines were negative. Tf was also synthesised by macrophages from congenitally hypotransferrinemic mice and was responsive to gamma-IFN, but levels were lower than those from normal controls. Synthesis by human and murine hepatoma cells was increased by IL-6 but unaffected by IL-1, TNF alpha, or gamma-IFN. Iron decreased synthesis by hepatoma cells but had no effect on the lymphomyeloid cells. Tf mRNA levels paralleled protein synthesis, suggesting that regulation was pre-translational. Thus, Tf synthesis by lymphomyeloid cells is regulated differently from hepatic synthesis, which is consistent with the suggestion that Tf may act in a paracrine (mouse) or autocrine (human) manner on activated lymphocytes.

Heme and Iron Metabolism: Role in Cerebral Hemorrhage

“…Transferrin is upregulated in microglia as well as astrocytes and oligodendrocytes following motor neuron injury (Tornquist et al, 1997). Cytokines, including TNF-␣, IL-1, and gamma interferon, induce transferrin in macrophages (Djeha et al, 1995), suggesting they might do the same in microglia and suggesting that transferrin might be an NF-B target gene.…”

Discovery and Qualification of Candidate Urinary Biomarkers of Disease Activity in Lupus Nephritis

“…Several proteins highlighted in this study have been previously reported to have biomarker utility in LN or other renal diseases, primarily as markers of renal histology or for diagnostic purposes. ,,,,, For example, one study found urinary transferrin and ceruloplasmin to be increased 3 months prior to renal flare, and furthermore, transferrin only increased in patients that flared, making it an intriguing prognostic biomarker candidate . Transferrin is important for the regulation of iron homeostasis and levels of transferrin are thought to be altered by cytokines like interferon-γ that are known to play a role in LN disease pathogenesis . A separate study identified urinary afamin and ceruloplasmin as prognostic biomarkers in IgA nephropathy patients, a common cause of primary glomerulonephritis …”

“…18 Transferrin is important for the regulation of iron homeostasis and levels of transferrin are thought to be altered by cytokines like interferon-γ that are known to play a role in LN disease pathogenesis. 48 A separate study identified urinary afamin and ceruloplasmin as prognostic biomarkers in IgA nephropathy patients, a common cause of primary glomerulonephritis. 34 This study is the first to describe urinary vimentin as a potential biomarker in LN.…”

Спороутворюючі Пробіотики, Дефіцит Заліза Та Імунітет

“…В биологическом смысле ТФ является аутокринным активатором лимфоцитов. Синтез ТФ человеческими лимфоцитами происходит под влиянием цитокинов: гамма-интерферона (-ИФН), интерлейкина-1 (ИЛ-1), ИЛ-6, фактора некроза опухоли альфа (ФНО-), причем данные цитокины усиливают синтез ТФ в следующей убывающей последовательности: -ИФН > ИЛ-1 > ИЛ-6 > ФНО- [38]. Доказано, что избыточное количество ИЛ-2 в сыворотке крови больных с опухолями или хроническими воспалительными заболеваниями ингибирует синтез ферритина в макрофагах, но стимулирует синтез ТФ, что увеличивает содержание железа в крови, но не в тканях (тканевый дефицит железа) (Lissoni P. еt al., 1993).…”