Up-regulation of Slc39A2(Zip2) mRNA in peripheral blood mononuclear cells from patients with pulmonary tuberculosis

Abstract

Zinc is the most common trace mineral after iron in the human body. In organisms, zinc transporters help zinc influx and efflux from cells. A previous study has reported that Zip2 was up-regulated over 27-fold in human monocytic THP-1 cells, when intracellular zinc was depleted by TPEN. Our study found Zip2 was over-expressed in leukocytes of asthmatic infants, especially those in which the serum zinc level was lower than those in healthy infants. Pulmonary tuberculosis (PTB) patients have significantly low serum zinc levels. Here we investigated whether Zip2 level was changed in the patients with PTB. Zip2 mRNA and protein levels in peripheral blood mononuclear cells (PBMC) from PTB (n1=23) and healthy controls (n2=42) were detected by quantitative real-time PCR and western blot, respectively. mRNA expression levels of another four zinc transporters, Zip1, Zip6, Zip8 and ZnT1, were detected by quantitative real-time PCR. Zip2 mRNA level was significantly up-regulated in PTB patients (P=0.001), and Zip8 mRNA level was significantly down-regulated compared with control individuals (P<0.001). In contrast, there were no significant changes in mRNA levels of Zip1, Zip6 and ZnT1 in either group (P>0.05). Zip2 protein expression levels increased in PTB patients compared with control individuals. Our study found that knockdown of ZIP2 with siRNA caused a decrease in Zip2 levels in PBMC of PTB patients, while reducing the expression of INF-γ (P<0.01) and increasing the expression of IL-6(P<0.01). These data provide evidence that increased expression of Zip2 gene is closely associated with immunity of PTB patients, suggesting that the Zip2 gene may play a key role in the initial infection control of the human body, by promoting and maintaining the immune response of adaptive T cells.

Effect of ZIP2 Gln/Arg/Leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation

“…Therefore, these findings strongly suggest a proinflammatory phenotype for Leu− subjects who also evidenced an increased expression of zinc transporters ZIP2, ZIP8 and Znt1. ZIP2 overexpression has been observed in PBMCs from patients with pulmonary infection or asthma and associated with an impaired zinc status . In the present investigation, ZIP2 upregulation in Leu− old donors, correlated to a slight reduction of the intracellular labile zinc but not with low plasma zinc.…”

“…Several studies suggest that ZIP2 may play a relevant role in the immune system especially during zinc deficiency , and it has been found to be the most sensitive zinc transporter in in vitro zinc depletion . On the other hand, ZIP2 overexpression is observed in patients with inflammatory diseases such as pulmonary infections and asthma characterized by peripheral zinc impairment .…”

Reassessment of the Transport Mechanism of the Human Zinc Transporter SLC39A2

“…Results were exported from the FLIPR raw data as "Area Under the Curve" (AUC) of the fluorescence signal intensity in the interval after the addition of substrates (seconds 460-750). In sodium replacement experiments 120 mM NaCl were replaced by 120 mM choline chloride, NMDG 5 or KCl. In chloride replacements assays all the chloride containing salts were replaced by their corresponding equimolar gluconate salts.…”

Malnutrition, Immunodeficiency, and Mucosal Infection

“…A number of zinc transporters have evolved to help zinc influx and efflux from cells. Recent studies indicate that upregulation of mRNA expression of Zip2 occurs when zinc is depleted from cells, such as leukocytes, during infection with pulmonary tuberculosis, and that Zip2 regulates expression of IFN-γ and IL-6, suggesting a mechanism of infection control (Tao et al, 2013). Zinc deficiency was first identified as a clinical syndrome of hypogonadism, stunting, and immune deficiency due to intake of dietary phytate in clay that blocked dietary absorption of zinc (Prasad, 2013).…”