Abstract
Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma.
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References
Ramos-Barbón, D., and A. Parra-Arrondo. 2011. Inflammation and remodeling of the distal airways: studies in humans and experimental models]. Archivos de Bronconeumología 47: 2.
Mauad, T., E.H. Bel, and P.J. Sterk. 2007. Asthma therapy and airway remodeling. Journal of Allergy and Clinical Immunology 120: 997–1009.
Homer, R.J., and J.A. Elias. 2005. Airway remodeling in asthma: therapeutic implications of mechanisms. Physiology 20: 28–35.
Shifren A, Witt C, Christie C, Castro M. Mechanisms of remodeling in asthmatic airways. Journal of allergy 2012; 2012.
Blumberg, H., D. Conklin, W. Xu, A. Grossmann, T. Brender, S. Carollo, et al. 2001. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104: 9–19.
Stenderup, K., C. Rosada, A. Worsaae, J.T. Clausen, and D.T. Norman. 2007. Interleukin‐20 as a target in psoriasis treatment. Annals of the New York Academy of Sciences 1110: 368–381.
Dumoutier, L., C. Leemans, D. Lejeune, S.V. Kotenko, and J.-C. Renauld. 2001. Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. The Journal of Immunology 167: 3545–3549.
Rich, B.E., and T.S. Kupper. 2001. Cytokines: IL-20—a new effector in skin inflammation. Current Biology 11: R531–R534.
Fonseca-Camarillo G, Furuzawa-Carballeda J, Llorente L, Yamamoto-Furusho JK. IL-10—and IL-20—expressing epithelial and inflammatory cells are increased in patients with ulcerative colitis. Journal of clinical immunology 2012:1-9.
Sa, S.M., P.A. Valdez, J. Wu, K. Jung, F. Zhong, L. Hall, et al. 2007. The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. The Journal of Immunology 178: 2229–2240.
Kragstrup, T.W., K. Otkjaer, C. Holm, A. Jørgensen, M. Hokland, L. Iversen, et al. 2008. The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy. Cytokine 41: 16–23.
Chen, W.-Y., B.-C. Cheng, M.-J. Jiang, M.-Y. Hsieh, and M.-S. Chang. 2006. IL-20 Is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E–deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology 26: 2090–2095.
Wei, C.-C., and M.-S. Chang. 2008. A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis. Genes and Immunity 9: 668–679.
Hsu, Y.H., H.H. Li, M.Y. Hsieh, M.F. Liu, K.Y. Huang, L.S. Chin, et al. 2006. Function of interleukin–20 as a proinflammatory molecule in rheumatoid and experimental arthritis. Arthritis & Rheumatism 54: 2722–2733.
Kim, S.J., J.-H. Shin, S.C. Kim, C.K. Park, and S.W. Kim. 2013. Preventive effects of oral tolerance on allergic inflammation and airway remodeling in a murine model. American Journal of Rhinology & Allergy 27: e11–e16.
Wu J, Liu F, Zhao J, Wei Y, Lv J, Dong F, et al. Thymic stromal lymphopoietin promotes asthmatic airway remodelling in human lung fibroblast cells through STAT3 signalling pathway. Cell biochemistry and function 2012.
Pestka, S., C.D. Krause, D. Sarkar, M.R. Walter, Y. Shi, and P.B. Fisher. 2004. Interleukin-10 and related cytokines and receptors. Annual Review of Immunology 22: 929–979.
Ouyang, W., S. Rutz, N.K. Crellin, P.A. Valdez, and S.G. Hymowitz. 2011. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annual Review of Immunology 29: 71–109.
Elias, J.A., Z. Zhu, G. Chupp, and R.J. Homer. 1999. Airway remodeling in asthma. Journal of Clinical Investigation 104: 1001–1006.
Litonjua, A.A., K.G. Tantisira, S. Lake, R. Lazarus, B.G. Richter, S. Gabriel, et al. 2005. Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma. Respiratory Research 6: 52.
Parrish-Novak, J., W. Xu, T. Brender, L. Yao, C. Jones, J. West, et al. 2002. Interleukins 19, 20, and 24 signal through two distinct receptor complexes differences in receptor-ligand interactions mediate unique biological functions. Journal of Biological Chemistry 277: 47517–47523.
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This research is supported by the National Nature Science Foundation of China (NSFC) (NSFC for LD, Grant No. 81270072), Natural Science Funding Committee of Shandong Province (SDNSF) (Grant No. ZR2011HM020), and Longhua Medical Project (RC). No potential conflicts of interest were disclosed.
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Wenbin Gong and Xin Wang are co-first authors.
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Gong, W., Wang, X., Zhang, Y. et al. Interleukin-20 Promotes Airway Remodeling in Asthma. Inflammation 37, 2099–2105 (2014). https://doi.org/10.1007/s10753-014-9944-8
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DOI: https://doi.org/10.1007/s10753-014-9944-8