Abstract
Inflammation of airway smooth muscle cells (ASMCs) is believed to be important in causing airway hyperresponsiveness. However, zinc has been reported to be implicated in many kinds of cell inflammation. Little is known about the effect of zinc treatment on Der p2 (group II Dermatophagoides pteronyssinus)-induced inflammation from ASMCs. This study investigated effects and mechanisms of zinc in Der p2-treated ASMCs. Der p2-treated primary ASMCs were cultured with various concentrations of zinc sulfate (ZnSO4) 6 μM, 12 μM, 24 μM, and 96 μM. The proteins and mRNAs of cytokines in ASMCs were examined by ELISA and real-time PCR. Intracellular zinc was stained with Zinquin fluorescence. The cell signaling protein expression was detected by Western blot. Der p2 was used to induce interleukin (IL)-6, IL-8, IL-1, and monocyte chemotactic protein-1 production of ASMCs. However, we found that 24 μM ZnSO4 reduced these inflammatory mediators production of Der p2-treated primary ASMCs. Der p2-induced extracellular signal-regulated kinases (ERK) and nuclear factor-kappa B (NF-κB) phosphorylation were suppressed by supplementation of 24 μM ZnSO4. Zinc is an anti-inflammatory agent that reduces inflammation of Der p2-treated ASMCs through the suppression of the ERK and NF-κB pathway. The results may be helpful for the development of effective treatments.
Similar content being viewed by others
Abbreviations
- ASMCs:
-
Airway smooth muscle cells
- AHR:
-
Airway hyperresponsiveness
- Der p2:
-
Group II Dermatophagoides pteronyssinus
- ERK:
-
Extracellular signal-regulated kinases
- NF-κB:
-
Nuclear factor-kappa B
- HBSS:
-
Hanks’ balanced salt solution
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- FBS:
-
Fetal bovine serum
- IL:
-
Interleukin
- MCP:
-
Monocyte chemotactic protein
- HDM:
-
House dust mite
- BSA:
-
Bovine serum albumin
- FBS:
-
Fetal bovine serum
- SDS:
-
Sodium dodecyl sulfate
References
Rabito, F.A., S. Iqbal, E. Holt, L.F. Grimsley, T.M. Islam, and S.K. Scott. 2007. Prevalence of indoor allergen exposures among New Orleans children with asthma. Journal of Urban Health 84: 782–792.
Tsai, J.J., H.D. Shen, and K.Y. Chua. 2000. Purification of group 2 Dermatophagoides pteronyssinus allergen and prevalence of its specific IgE in asthmatics. International Archives of Allergy and Immunology 121: 205–210.
Roche, N., T.C. Chinet, and G.J. Huchon. 1997. Allergic and nonallergic interactions between house dust mite allergens and airway mucosa. European Respiratory Journal 10: 719–726.
Seersholm, N., and A. Kok-Jensen. 1995. Survival in relation to lung function and smoking cessation in patients with severe hereditary alpha 1-antitrypsin deficiency. American Journal of Respiratory and Critical Care Medicine 151: 369–373.
Sukkar, M.B., S. Xie, N.M. Khorasani, O.M. Kon, R. Stanbridge, R. Issa, and K.F. Chung. 2006. Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle. The Journal of Allergy and Clinical Immunology 118: 641–648.
Panettieri Jr., R.A. 2004. Airway smooth muscle: immunomodulatory cells? Allergy and Asthma Proceedings 25: 381–386.
Grunstein, M.M., H. Veler, X. Shan, J. Larson, J.S. Grunstein, and S. Chuang. 2005. Proasthmatic effects and mechanisms of action of the dust mite allergen, Der p 1, in airway smooth muscle. The Journal of Allergy and Clinical Immunology 116: 94–101.
Chiou, Y.L., and C.Y. Lin. 2009. Der p2 activates airway smooth muscle cells in a TLR2/MyD88-dependent manner to induce an inflammatory response. Journal of Cellular Physiology 220: 311–318.
de Luis, D.A., O. Izaola, R. Aller, A. Armentia, and L. Cuellar. 2003. [Antioxidant and fat intake in patients with polinic asthma]. Med Clin (Barc) 121: 653–654.
Soutar, A., A. Seaton, and K. Brown. 1997. Bronchial reactivity and dietary antioxidants. Thorax 52: 166–170.
Tahan, F., and C. Karakukcu. 2006. Zinc status in infantile wheezing. Pediatric Pulmonology 41: 630–634.
Truong-Tran, A.Q., R.E. Ruffin, P.S. Foster, A.M. Koskinen, P. Coyle, J.C. Philcox, A.M. Rofe, and P.D. Zalewski. 2002. Altered zinc homeostasis and caspase-3 activity in murine allergic airway inflammation. American Journal of Respiratory Cell and Molecular Biology 27: 286–296.
Lichten, L.A., and R.J. Cousins. 2009. Mammalian zinc transporters: nutritional and physiologic regulation. Annual Review of Nutrition 29: 153–176.
Lang, C., C. Murgia, M. Leong, L.W. Tan, G. Perozzi, D. Knight, R. Ruffin, and P. Zalewski. 2007. Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. American Journal of Physiology. Lung Cellular and Molecular Physiology 292: L577–584.
Murgia, C., C.J. Lang, A.Q. Truong-Tran, D. Grosser, L. Jayaram, R.E. Ruffin, G. Perozzi, and P.D. Zalewski. 2006. Zinc and its specific transporters as potential targets in airway disease. Current Drug Targets 7: 607–627.
Devereux, G., S.W. Turner, L.C. Craig, G. McNeill, S. Martindale, P.J. Harbour, P.J. Helms, and A. Seaton. 2006. Low maternal vitamin E intake during pregnancy is associated with asthma in 5-year-old children. American Journal of Respiratory and Critical Care Medicine 174: 499–507.
Barnes, P.J., S. Pedersen, and W.W. Busse. 1998. Efficacy and safety of inhaled corticosteroids. New developments. American Journal of Respiratory and Critical Care Medicine 157: S1–53.
Pauwels, R.A., C.G. Lofdahl, D.S. Postma, A.E. Tattersfield, P. O'Byrne, P.J. Barnes, and A. Ullman. 1997. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. The New England Journal of Medicine 337: 1405–1411.
Ellul-Micallef, R., A. Galdes, and F.F. Fenech. 1976. Serum zinc levels in corticosteroid-treated asthmatic patients. Postgraduate Medical Journal 52: 148–150.
Guo, C.H., P.J. Liu, K.P. Lin, and P.C. Chen. 2012. Nutritional supplement therapy improves oxidative stress, immune response, pulmonary function, and quality of life in allergic asthma patients: an open-label pilot study. Alternative Medicine Review 17: 42–56.
Prasad, A.S. 2000. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. Journal of Infectious Diseases 182(Suppl 1): S62–68.
Truong-Tran, A.Q., L.H. Ho, F. Chai, and P.D. Zalewski. 2000. Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell death. Journal of Nutrition 130: 1459S–1466S.
Carter, J.E., A.Q. Truong-Tran, D. Grosser, L. Ho, R.E. Ruffin, and P.D. Zalewski. 2002. Involvement of redox events in caspase activation in zinc-depleted airway epithelial cells. Biochemical and Biophysical Research Communications 297: 1062–1070.
Powell, S.R. 2000. The antioxidant properties of zinc. Journal of Nutrition 130: 1447S–1454S.
Truong-Tran, A.Q., D. Grosser, R.E. Ruffin, C. Murgia, and P.D. Zalewski. 2003. Apoptosis in the normal and inflamed airway epithelium: role of zinc in epithelial protection and procaspase-3 regulation. Biochemical Pharmacology 66: 1459–1468.
Hennig, B., P. Meerarani, P. Ramadass, M. Toborek, A. Malecki, R. Slim, and C.J. McClain. 1999. Zinc nutrition and apoptosis of vascular endothelial cells: implications in atherosclerosis. Nutrition 15: 744–748.
Novick, S.G., J.C. Godfrey, R.L. Pollack, and H.R. Wilder. 1997. Zinc-induced suppression of inflammation in the respiratory tract, caused by infection with human rhinovirus and other irritants. Medical Hypotheses 49: 347–357.
Paramanantham, R., B.H. Bay, and K.H. Sit. 1996. Flow cytometric evaluation of the DNA profile and cell cycle of zinc supplemented human Chang liver cells. Acta Paediatrica Japonica 38: 334–338.
Prasad, A.S., B. Bao, F.W. Beck, and F.H. Sarkar. 2011. Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-kappaB. Nutrition 27: 816–823.
von Bulow, V., L. Rink, and H. Haase. 2005. Zinc-mediated inhibition of cyclic nucleotide phosphodiesterase activity and expression suppresses TNF-alpha and IL-1 beta production in monocytes by elevation of guanosine 3′,5′-cyclic monophosphate. Journal of Immunology 175: 4697–4705.
Acknowledgment
The authors would like to thank the National Science Council (project number 99-2320-B-241-001) and the Institute of BioMedical Nutrition, Hungkuang University for financially supporting this research. The sole author had responsibility for all parts of the manuscript.
The authors have no conflicts of interest to disclose, whether financial or of any other nature.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shih, CJ., Chiou, YL. Zinc Sulfate Inhibited Inflammation of Der p2-Induced Airway Smooth Muscle Cells by Suppressing ERK1/2 and NF-κB Phosphorylation. Inflammation 36, 616–624 (2013). https://doi.org/10.1007/s10753-012-9583-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-012-9583-x