Expression of surfactant protein D in airways of asthmatics and interleukin-13 modulation of surfactant protein D in human models of airway epithelium

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• 作者：Jie Xu ; Gurpreet K Singhera ; Delbert R Dorscheid
• 关键词：Surfactant protein D ; Asthma ; Airway epithelium ; Air ; liquid ; interface ; Interleukin ; 13
• 刊名：Respiratory Research
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：16
• 期：1
• 全文大小：1,271 KB
• 参考文献：1. The International Union Against Tuberculosis and Lung Disease. The Global Asthma Report. Paris; 2011. ISBN Number: 978-2-914365-83-3.
  2. Davies, DE, Wicks, J, Powell, RM, Puddicombe, SM, Holgate, ST (2003) Airway remodeling in asthma: new insights. J Allergy Clin Immunol 111: pp. 215-25 CrossRef
  3. Hackett, TL, Singhera, GK, Shaheen, F, Hayden, P, Jackson, GR, Hegele, RG (2011) Intrinsic phenotypic differences of asthmatic epithelium and its inflammatory responses to respiratory syncytial virus and air pollution. Am J Respir Cell Mol Biol 45: pp. 1090-100 CrossRef
  4. Busse, WW, Lemanske, RF, Gern, JE (2010) Role of viral respiratory infections in asthma and asthma exacerbations. Lancet 376: pp. 826-34 CrossRef
  5. Nair, H, Nokes, DJ, Gessner, BD, Dherani, M, Madhi, SA, Singleton, RJ (2010) Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 375: pp. 1545-55 CrossRef
  6. Sigurs, N, Bjarnason, R, Sigurbergsson, F, Kjellman, B (2000) Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 161: pp. 1501-7 CrossRef
  7. Sigurs, N, Gustafsson, PM, Bjarnason, R, Lundberg, F, Schmidt, S, Sigurbergsson, F (2005) Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med 161: pp. 137-41 CrossRef
  8. Henderson, J, Hilliard, TN, Sherriff, A, Stalker, D, Al Sammari, N, Thomas, HM (2005) Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: a longitudinal birth cohort study. Pediatr Allergy Immunol 16: pp. 386-92 CrossRef
  9. Bont, L, Stejin, M, Aalderen, WM, Brus, F, Th Draaisma, JM, Diemen-Steenvoorde, RA (2004) Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection. Thorax 59: pp. 512-6 CrossRef
  10. Holtzman, MJ (2012) Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest 122: pp. 2741-8 CrossRef
  11. Wright, JR (2005) Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5: pp. 58-68 CrossRef
  12. Wang, JY, Reid, KB (2007) The immunoregulatory roles of lung surfactant collectins SP-A, and SP-D, in allergen-induced airway inflammation. Immunobiology 212: pp. 417-25 CrossRef
  13. Wills-Karp, M (2004) Interleukin-13 in asthma pathogenesis. Immunol Rev 202: pp. 175-90 CrossRef
  14. Hancock, A, Armstrong, L, Gama, R, Millar, A (1998) Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am J Respir Cell Mol Biol 18: pp. 60-5 CrossRef
  15. Burd, PR, Thompson, WC, Max, EE, Mills, FC (1995) Activated mast cells produce interleukin 13. J Exp Med 181: pp. 1373-80 CrossRef
  16. Grunig, G, Warnock, M, Wakil, AE, Venkayya, R, Brombacher, F, Rennick, DM (1998) Requirement for IL-13 independently of IL-4 in experimental asthma. Science 282: pp. 2261-3 CrossRef
  17. Zhu, Z, Homer, RJ, Wang, Z, Chen, Q, Geba, GP, Wang, J (19
• 刊物主题：Pneumology/Respiratory System;
• 出版者：BioMed Central
• ISSN：1465-9921

文摘

Background Surfactant protein D (SP-D), a pattern recognition molecule, has been shown to play roles in host defense such as opsonisation, aggregation of pathogens, and modulation of the inflammatory response. In light of infection-induced exacerbations and damage to the airway epithelium from inflammation, these functions of SP-D make it relevant in the development and pathogenesis of asthma. Methods Expression of SP-D was examined in human airway sections and primary airway epithelial cells (AEC) grown in air-liquid interface (ALI) cultures and comparisons were made between those from asthmatic and non-asthmatic donors. ALI cultures of AEC from non-asthmatic donors were examined for SP-D, Mucin 5AC, and cytokeratin-5 expression at different stages of differentiation. Interleukin-13 (IL-13) treatment of airway epithelium and its effect on SP-D expression was studied using ALI and monolayer cultures of primary AEC from non-asthmatic and asthmatic donors. Results Airway epithelium of asthmatics, compared to that of non-asthmatics, expressed increased levels of SP-D as demonstrated in airway tissue sections (fraction of epithelium 0.66 ± 0.026 vs. 0.50 ± 0.043, p = 0.004) and ALI cultures (fraction of epithelium 0.50 ± 0.08 vs. 0.25 ± 0.07). SP-D expression decreased as ALI cultures differentiated from 7 days to 21 days (fraction of epithelium 0.62 ± 0.04 to 0.23 ± 0.03, p = 0.004). Treatment with IL-13 decreased SP-D expression in both ALI cultures (fraction of epithelium 0.21 ± 0.06 vs. 0.62 ± 0.04, p = 0.0005) and monolayer cultures (protein expression fold change 0.62 ± 0.05) of non-asthmatic AEC; however, IL-13 had no significant effect on SP-D expression in monolayer cultures of asthmatic AEC. Experiments with non-asthmatic monolayer cultures indicate IL-13 exert its effect on SP-D through the IL-13 receptor alpha1 and transcription factor STAT6. Conclusions SP-D is expressed differently in airways of asthmatics relative to that of non-asthmatics. This can have implications on the increased susceptibility to infections and altered inflammatory response in asthmatic patients. Future functional studies on the role of SP-D in asthma can provide better insight into defects in the structure and regulation of SP-D.