Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation.
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 (Truong-Tran AQ, Ruffin RE, Foster PS, Koskinen AM, Coyle P, Philcox JC, Rofe AM, Zalewski PD. Am J Respir Cell Mol Biol 27: 286-296, 2002). Moreover, mild nutritional Zn deficiency worsens lung function. Recently, a number of proteins belonging to the Solute Carrier Family 39 (ZIP) and Solute Carrier Family 30 (ZnT) 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 100 microg of Zn intraperitoneally. Tissues were analyzed for Zn content and histopathology. Inflammatory cells were counted in bronchoalveolar lavage fluid. Cytokine and Zn transporter mRNA levels were determined by cDNA gene array and/or real-time PCR. Zn supplementation decreased bronchoalveolar lavage fluid 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 it did not affect mRNA levels of cytokines or their receptors. Our results indicate that inflammation-induced alterations in Zn transporter gene expression are directed toward 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 asthmatic individuals.
Lang
Carol
C
Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia, Australia. carol.lang@adelaide.edu.au
Murgia
Chiara
C
Leong
Mary
M
Tan
Lor-Wai
LW
Perozzi
Giuditta
G
Knight
Darryl
D
Ruffin
Richard
R
Zalewski
Peter
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000473:pathology*; D015032:Zinc / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D027682:Cation Transport Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D008668:Metallothionein; D015032:Zinc