title: Tumour necrosis factor-alpha transcription in transferrin-stimulated human blood mononuclear cells: is transferrin receptor involved in the signalling mechanism?
abstract: Transferrin (Tf) and tumour necrosis factor-alpha (TNF-alpha) participate in immune response regulation. We studied the capacity of Tf to modulate 'in vitro' TNF-alpha secretion, membrane expression and transcription by human blood mononuclear cells (BMNC). Women 25-45 years of age with normal iron status (n = 20) or with iron deficiency (ID, n = 20) due to gynaecological bleeding were studied. BMNC were incubated with different proportions of Fe-exempt and Fe-saturated Tf (apo-Tf:holo-Tf). Apo-Tf or holo-Tf uniformly induced TNF-alpha secretion in the cell supernatants from both groups. Nevertheless, cytokine levels were significantly lower in ID subjects. For all Tf-Fe saturations assayed, mean TNF-alpha levels varied between 1.4-1.6 ng/ml and 0.4-0.7 ng/ml for normal and ID women respectively (P < 0.001). The addition of apo-Tf enhanced TNF-alpha secretion in a dose-dependent manner, but the cytokine levels were lower in ID group. Tf did not induce pro-TNF-alpha expression in monocytes and lymphocytes from either group. Tf-treated cells from normal individuals expressed approximately two to three times more TNF-alpha mRNA than cells from ID subjects. Mean values ranged 96-110 atmol/ml in normal women and 24-31 atmol/ml in ID women for all Tf-Fe saturation levels tested (P < 0.001). These results show that Tf-induced TNF-alpha secretion is transcriptionally regulated. The impaired TNF-alpha transcription in cells from ID subjects indicates that the quality of the immune response is linked to the Fe status of mononuclear cells.
authors.affiliation: Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Lopez
authors.forename: Ernesto
authors.initials: E
authors.lastname: Rios
authors.forename: Liana
authors.initials: L
authors.lastname: Schlesinger
authors.forename: Manuel
authors.initials: M
authors.lastname: Olivares
authors.forename: Marco T
authors.initials: MT
authors.lastname: Nunez
authors.forename: Carlos
authors.initials: C
authors.lastname: Munoz
mesh_terms: D000328:Adult; D001051:Apoenzymes / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000090463:Iron Deficiencies; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism*; D013925:Thromboplastin / Q000494:pharmacology; D014168:Transferrin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D001051:Apoenzymes; C052493:F3 protein, human; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin