Dietary zinc mediates inflammation and protects against wasting and metabolic derangement caused by sustained cigarette smoke exposure in mice
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In mouse asthma models, inflammation can be modulated by zinc (Zn). Given that appetite loss, muscle wasting and poor nutrition are features of chronic obstructive pulmonary disease (COPD) and that poor dietary Zn intake is in itself accompanied by growth retardation and appetite loss, we hypothesised that dietary Zn limitation would not only worsen airway inflammation but also exaggerate metabolic effects of cigarette smoke (CS) exposure in mice. Conversely, Zn supplementation would lessen inflammation. Mice were exposed to CS [2× 2RF, 3×/day; 15 min/cigarette] and fed diets containing 2, 20 or 140 mg/kg Zn ad libitum. Airway cells were collected by bronchoalveolar lavage (BAL). Plasma Zn was measured by fluorometric assay. Inflammatory, metabolic and Zn transport markers were measured by real-time RT-PCR. Mice fed low Zn diets had less plasma labile zinc (0–0.18 μM) than mice fed moderate (0.61–0.98 μM) or high (0.77–1.1 μM) Zn diets (SDs 0.1–0.4, n = 8–10). Smoke exposure increased plasma and BAL labile Zn (1.5–2.5 fold, P < 0.001), bronchoalveolar macrophages (2.0 fold, P < 0.0001) and MT-1 (1.5 fold), MIP-2 (2.3 fold) and MMP-12 (3.5 fold) mRNA. Zn supplementation reduced alveolar macrophage numbers by 62 and 52% in sham and smoke-exposed mice, respectively (Zn effect: P = 0.011). Gastrocnemius, soleus and tibialis anterior muscle mass were affected by both smoke and dietary Zn in the order of 3–7%. The 50–60% reduction in alveolar macrophages in Zn-supplemented mice supports our evolving hypothesis that Zn is an important anti-inflammatory mediator of airway inflammation. Restoring airway Zn levels through dietary supplementation may lessen the severity of lung inflammation when Zn intake is low.
KeywordsZinc Zinc transporters Cigarette smoke Chronic Obstructive Pulmonary Disease (COPD) Inflammation Metabolic wasting
The authors are grateful to Dr Peter Coyle for advice and equipment pertaining to atomic adsorption for zinc measurements and to staff at the Queen Elizabeth Hospital Animal house. Prof Leigh Ackland from Deakin University is gratefully acknowledged for her gift of the sheep anti-mouse ZIP1 antibody. Rhys Hamon is thanked for his involvement in optimising and performing the ZIP1 westerns. Sook Ching Lee and Mary Leong are thanked for technical assistance early in the project. This research is supported by the National Health and Medical Research Council of Australia and The Queen Elizabeth Hospital Research Foundation. Dr Lang was the grateful recipient of an Australian Lung Foundation/Boehringer Ingelheim Chronic Airflow Limitation Research Fellowship and currently holds a NHMRC Australian Biomedical (Peter Doherty) Training Fellowship.
- Chen H, Vlahos R, Bozinovski S, Jones J, Anderson GP, Morris MJ (2004) Effect of short-term cigarette smoke exposure on body weight, appetite and brain neuropeptide Y in mice. Neuropsychopharmacology 30(4):69–75Google Scholar
- Haughney, van der Molen (2005) http://www.azair.com/timetolive
- Suzuki T, Ishihara K, Migaki H, Nagao M, Yamaguchi-Iwai Y, Kambe T (2005) Two different zinc transport complexes of cation diffusion facilitator proteins localized in the secretory pathway operate to activate alkaline phosphatases in vertebrate cells. J Biol Chem 280(35):30956–30962CrossRefPubMedGoogle Scholar