Tumour necrosis factor ot causes hypoferraemia and reduced intestinal iron absorption in mice
Tumour necrosis factor ot causes hypoferraemia and reduced intestinal iron absorption in mice
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DOI：
10.1042/bj20060215
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发表时间：
2006-07-01
影响因子：
4.1
通讯作者：
Tselepis, Chris
中科院分区：
文献类型：
--
作者：
Laftah, Abas H.;Sharma, Naveen;Tselepis, Chris
细胞因子通过减少红细胞生成和增加网状内皮系统中铁的固存而与慢性疾病的贫血有关。然而，细胞因子，特别是肿瘤坏死因子α对小肠铁摄取和铁转运体表达的影响尚不清楚。在本研究中，我们给CD-I雄性小鼠腹腔注射肿瘤坏死因子α(10 ng/只)，然后检测DMTI(二价金属转运蛋白1)、IREG1(铁调节蛋白1)和铁蛋白在十二指肠中的表达和定位。取小鼠肝、脾组织，检测肝组织中海普西丁基因的表达。测定血清铁和十二指肠、脾、肝铁负荷的变化。我们发现在肿瘤坏死因子α暴露后3小时，血清铁显著下降(P<；0.05)。这与脾中铁沉积的增加是一致的。暴露24 h后，十二指肠铁转运量显著减少(P<；0.05)，肠细胞铁蛋白表达增加(P<；0.05)，IREG1从基侧肠细胞膜重新定位。结果表明，肿瘤坏死因子α可能通过减少十二指肠铁转运而导致慢性疾病贫血，这可能是由于铁蛋白增加了肠细胞铁结合力，IREG1功能丧失所致。这些观察结果与海普西丁的mRNA水平无关。
Cytokines are implicated in the anaemia of chronic disease by reducing erythropoiesis and increasing iron sequestration in the reticuloendotheial system. However, the effect of cytokines, in particular TNF alpha (tumour necrosis factor alpha), on small bowel iron uptake and iron-transporter expression remains unclear. In the present study, we subjected CD I male mice to intraperitoneal injection with TNF alpha (10 ng/mouse) and then examined the expression and localization of DMTI (divalent metal transporter 1), IREG1 (iron-regulated protein 1) and ferritin in duodenum. Liver and spleen samples were used to determine hepcidin mRNA expression. Changes in serum iron and iron loading of duodenum, spleen and liver were also determined. We found a significant (P < 0.05) fall in serum iron 3 h post-TNF alpha exposure. This was coincident with increased iron deposition in the spleen. After 24 h of exposure, there was a significant decrease in duodenal iron transfer (P < 0.05) coincident with increased enterocyte ferritin expression (P < 0.05) and re-localization of IREG1 from the basolateral enterocyte membrane. Hepatic hepcidin mRNA levels remained unchanged, whereas splenic hepcidin mRNA expression was reduced at 24 h. In conclusion, we provide evidence that TNF alpha may contribute to anaemia of chronic disease by iron sequestration in the spleen and by reduced duodenal iron transfer, which seems to be due to increased enterocyte iron binding by ferritin and a loss of IREG1 function. These observations were independent of hepcidin mRNA levels.