Iron deficiency is common throughout the world and has been linked to immunity impairments. Using piglets to model human infants, we assessed the impact of systemic iron homeostasis on proinflammatory status. Artificially reared piglets were parenterally supplied with iron dextran by intramuscular administration at the age of 3 days. Relative to no iron supplementation (control), iron dextran-treated (FeDex) piglets increased hematological parameters as well as iron levels in serum and tissues from days 21 to 49. High expression of hepcidin was observed in FeDex-treated piglets, which correlated with suppressed expression of ferroportin in duodenum. Lower levels of proinflammatory cytokine (IL-6, TNF-α, IFN-γ, and IL-1β) transcripts were detected in ileum of FeDex-treated piglets, which indicated that iron supplementation could attenuate the increase of inflammatory cytokines caused by iron deficiency. Histopathological analysis of liver and duodenum proved the less inflammatory responses after iron supplementation. Hepcidin was highly stimulated by FeDex supplementation and attenuated the inflammation of anemia, which implied that hepcidin might had antiinflammatory function and is a candidate regulator of the cross-talk between iron regulation and inflammation.
Early nutrition is key to promoting gut growth and education of the immune system. Although iron deficiency anemia has long been recognized as a serious iron disorder, the effects of iron supplementation on gut development are less clear. Therefore, using suckling piglets as the model for iron deficiency, we assessed the impacts of iron supplementation on hematological status, gut development, and immunity improvement. Piglets were parenterally supplied with iron dextran (FeDex, 60 mg Fe/kg) by intramuscular administration on the third day after birth and slaughtered at the age of two days, five days, 10 days, and 20 days. It was expected that iron supplementation with FeDex improved the iron status with higher levels of serum iron, ferritin, transferrin, and iron loading in the liver by regulating the interaction of hepcidin and ferroportin (FPN). FeDex supplementation increased villus length and crypt depth, attenuated the pathological status of the duodenum, and was beneficial to intestinal mucosa. FeDex also influenced the intestinal immune development by stimulating the cytokines’ production of the intestine and enhancing the phagocytotic capacity of monocytes. Overall, the present study suggested that iron supplementation helped promote the development of the intestine by improving its morphology, which maintains its mucosal integrity and enhances the expression of immuno-associated factors.
Hepcidin was first identified as an antimicrobial peptide and later demonstrated that hepcidin is the long sought hormone to regulate iron homeostasis in mammals. Though its iron regulatory function has been extensively investigated, the studies on its antimicrobial properties are limited. The aim of current study was to evaluate the antibacterial activity of synthetic porcine hepcidin (pHepc) in vitro against pathogen bacteria via radial diffusion, colony forming count, transmission electron microscopy and DNA binding assays. Our results showed that pHepc exerted little bactericidal activity, but possessed bacteriostatic activity by reducing the viable Escherichia coli K88, E. coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Salmonella typhimurium CMCC 50013. pHepc-treated E. coli K88 exhibited longer cells and cytoplasm unevenly distribution, while pHepc-treated S. aureus led to cytoplasm leakage and partly lysis of bacterial cells. Gel retardation assay showed the existence of the binding affinity of pHepc for DNA. In addition, pHepc retained the bacteriostatic activity in a wide range of pH value from 4.0 to 8.0 or in the presence of iron, respectively. Considering the high expression in response to infection and the bacteriostatic activity, pHepc may be an important defense molecule for pig health.
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