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1 Medicine, University of Adelaide, Adelaide, South Australia, Australia
2 Experimental Nutrition, National Research Institute for Food and Nutrition, Rome, Italy
3 Surgery, University of Adelaide, Adelaide, South Australia, Australia
4 Canada Research Chair in Airway Disease & Department of Pharmacology, University of British Columbia, Vancouver, Canada
5 Medicine, University of Adelaide, Woodville, South Australia, Australia
* To whom correspondence should be addressed. E-mail: carol.lang{at}adelaide.edu.au.
There is clinical evidence linking asthma with the trace element, zinc (Zn). Using a mouse model of allergic inflammation, we have previously shown that labile Zn decreases in inflamed airway epithelium. Moreover, mild nutritional Zn deficiency worsens lung function. Recently, a number of proteins belonging to ZIP and ZnT families have been identified that bind Zn and regulate Zn homeostasis. Mice were sensitized, and subsequently aerochallenged, with ovalbumin to induce acute and chronic airway inflammation. Mice received 0, 54 or 100µg of Zn intraperitoneally. Tissues were analysed for Zn content and histopathology. Inflammatory cells were counted in bronchoalveolar lavage fluid (BAL). Cytokine and Zn transporter mRNA levels were determined by cDNA gene array and/or real-time PCR. Zn supplementation decreased BAL eosinophils by 40 and 80%, and lymphocytes by 55 and 66%, in the acute and chronic models, respectively. Alterations in Zn transporter expression were observed during acute inflammation, including increases in ZIP1 and ZIP14 and decreases in ZIP4 and ZnT4. Zn supplementation normalized ZIP1 and ZIP14, but did not affect mRNA levels of cytokines or their receptors. Our results indicate that inflammation-induced alterations in Zn transporter gene expression are directed towards increasing Zn uptake. Increases in Zn uptake may be needed to counteract the local loss of Zn in the airway and to meet an increased demand for Zn-dependent proteins. The reduction of inflammatory cells by Zn in the airways provides support for Zn supplementation trials in human asthmatics.
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