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Published in: Respiratory Research 1/2010

Open Access 01-12-2010 | Research

Elevated expression of both mRNA and protein levels of IL-17A in sputum of stable Cystic Fibrosis patients

Authors: Ann Decraene, Anna Willems-Widyastuti, Ahmad Kasran, Kris De Boeck, Dominique M Bullens, Lieven J Dupont

Published in: Respiratory Research | Issue 1/2010

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Abstract

Background

T helper 17 (Th17) cells can recruit neutrophils to inflammatory sites through production of IL-17, which induces chemokine release. IL-23 is an important inducer of IL-17 and IL-22 production. Our aim was to study the role of Th17 cells in cystic fibrosis (CF) lung disease by measuring IL-17 protein and mRNA levels and IL-22 and IL-23 mRNA in sputum of clinically stable CF patients and by comparing these levels with healthy controls.

Methods

Sputum induction was performed in adult CF patients outside of an exacerbation and healthy control subjects. IL-17A protein levels were measured in supernatants with cytometric bead array (CBA) and RNA was isolated and quantitative RT-PCR was performed for IL-17A, IL-22 and IL-23.

Results

We found significantly higher levels of IL-17A protein and mRNA levels (both: p < 0.0001) and IL-23 mRNA levels (p < 0.0001) in the sputum of CF group as compared to controls. We found very low levels of IL-22 mRNA in the CF group. The levels of IL-17 and IL-23 mRNA were higher in patients chronically infected with Pseudomonas aeruginosa (P. aeruginosa) as compared to those who were not chronically infected with P. aeruginosa. The presence of Staphylococcus aureus (S. aureus) on sputum did not affect the IL-17 or IL-23 levels. There was no correlation between IL-17 or IL-23 levels and FEV1 nor sputum neutrophilia.

Conclusion

The elevated levels of IL-17 and IL-23 might indicate that Th17 cells are implicated in the persistent neutrophil infiltration in CF lung disease and chronic infection with P. aeruginosa.
Literature
3.
go back to reference Hubeau C, Lorenzato M, Couetil JP, Hubert D, Dusser D, Puchelle E, et al.: Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa. Clin Exp Immunol 2001,124(1):69–76.CrossRefPubMedPubMedCentral Hubeau C, Lorenzato M, Couetil JP, Hubert D, Dusser D, Puchelle E, et al.: Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa. Clin Exp Immunol 2001,124(1):69–76.CrossRefPubMedPubMedCentral
4.
go back to reference Wojnarowski C, Frischer T, Hofbauer E, Grabner C, Mosgoeller W, Eichler I, et al.: Cytokine expression in bronchial biopsies of cystic fibrosis patients with and without acute exacerbation. Eur Respir J 1999,14(5):1136–44.CrossRefPubMed Wojnarowski C, Frischer T, Hofbauer E, Grabner C, Mosgoeller W, Eichler I, et al.: Cytokine expression in bronchial biopsies of cystic fibrosis patients with and without acute exacerbation. Eur Respir J 1999,14(5):1136–44.CrossRefPubMed
5.
6.
go back to reference Moser C, Jensen PO, Pressler T, Frederiksen B, Lanng S, Kharazmi A, et al.: Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. APMIS 2005,113(6):400–9.CrossRefPubMed Moser C, Jensen PO, Pressler T, Frederiksen B, Lanng S, Kharazmi A, et al.: Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. APMIS 2005,113(6):400–9.CrossRefPubMed
7.
go back to reference Lankford CS, Frucht DM: A unique role for IL-23 in promoting cellular immunity. J Leukoc Biol 2003,73(1):49–56.CrossRefPubMed Lankford CS, Frucht DM: A unique role for IL-23 in promoting cellular immunity. J Leukoc Biol 2003,73(1):49–56.CrossRefPubMed
8.
go back to reference Kawaguchi M, Adachi M, Oda N, Kokubu F, Huang SK: IL-17 cytokine family. J Allergy Clin Immunol 2004,114(6):1265–73.CrossRefPubMed Kawaguchi M, Adachi M, Oda N, Kokubu F, Huang SK: IL-17 cytokine family. J Allergy Clin Immunol 2004,114(6):1265–73.CrossRefPubMed
9.
go back to reference Bullens DM, Truyen E, Coteur L, Dilissen E, Hellings PW, Dupont LJ, et al.: IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res 2006, 7:135.CrossRefPubMedPubMedCentral Bullens DM, Truyen E, Coteur L, Dilissen E, Hellings PW, Dupont LJ, et al.: IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res 2006, 7:135.CrossRefPubMedPubMedCentral
10.
go back to reference Vanaudenaerde BM, De Vleeschauwer SI, Vos R, Meyts I, Bullens DM, Reynders V, et al.: The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant 2008,8(9):1911–20.CrossRefPubMed Vanaudenaerde BM, De Vleeschauwer SI, Vos R, Meyts I, Bullens DM, Reynders V, et al.: The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant 2008,8(9):1911–20.CrossRefPubMed
11.
12.
go back to reference Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, et al.: Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006,203(10):2271–9.CrossRefPubMedPubMedCentral Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, et al.: Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006,203(10):2271–9.CrossRefPubMedPubMedCentral
13.
go back to reference Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, et al.: IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 2008,14(3):275–81.CrossRefPubMedPubMedCentral Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, et al.: IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 2008,14(3):275–81.CrossRefPubMedPubMedCentral
14.
go back to reference McAllister F, Henry A, Kreindler JL, Dubin PJ, Ulrich L, Steele C, et al.: Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J Immunol 2005,175(1):404–12.CrossRefPubMedPubMedCentral McAllister F, Henry A, Kreindler JL, Dubin PJ, Ulrich L, Steele C, et al.: Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J Immunol 2005,175(1):404–12.CrossRefPubMedPubMedCentral
15.
go back to reference Lee TW, Brownlee KG, Conway SP, Denton M, Littlewood JM: Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2003,2(1):29–34.CrossRefPubMed Lee TW, Brownlee KG, Conway SP, Denton M, Littlewood JM: Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2003,2(1):29–34.CrossRefPubMed
16.
go back to reference Proesmans M, Balinska-Miskiewicz W, Dupont L, Bossuyt X, Verhaegen J, Hoiby N, et al.: Evaluating the "Leeds criteria" for Pseudomonas aeruginosa infection in a cystic fibrosis centre. Eur Respir J 2006,27(5):937–43.PubMed Proesmans M, Balinska-Miskiewicz W, Dupont L, Bossuyt X, Verhaegen J, Hoiby N, et al.: Evaluating the "Leeds criteria" for Pseudomonas aeruginosa infection in a cystic fibrosis centre. Eur Respir J 2006,27(5):937–43.PubMed
17.
go back to reference Truyen E, Coteur L, Dilissen E, Overbergh L, Dupont LJ, Ceuppens JL, et al.: Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients. Thorax 2006,61(3):202–8.CrossRefPubMedPubMedCentral Truyen E, Coteur L, Dilissen E, Overbergh L, Dupont LJ, Ceuppens JL, et al.: Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients. Thorax 2006,61(3):202–8.CrossRefPubMedPubMedCentral
18.
go back to reference Pizzichini E, Pizzichini MM, Efthimiadis A, Hargreave FE, Dolovich J: Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination. Eur Respir J 1996,9(6):1174–80.CrossRefPubMed Pizzichini E, Pizzichini MM, Efthimiadis A, Hargreave FE, Dolovich J: Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination. Eur Respir J 1996,9(6):1174–80.CrossRefPubMed
19.
go back to reference Eickmeier O, Huebner M, Herrmann E, Zissler U, Rosewich M, Baer PC, et al.: Sputum biomarker profiles in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) and association between pulmonary function. Cytokine 2010. Eickmeier O, Huebner M, Herrmann E, Zissler U, Rosewich M, Baer PC, et al.: Sputum biomarker profiles in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) and association between pulmonary function. Cytokine 2010.
20.
go back to reference Dubin PJ, McAllister F, Kolls JK: Is cystic fibrosis a TH17 disease? Inflamm Res 2007,56(6):221–7.CrossRefPubMed Dubin PJ, McAllister F, Kolls JK: Is cystic fibrosis a TH17 disease? Inflamm Res 2007,56(6):221–7.CrossRefPubMed
21.
go back to reference Dubin PJ, Kolls JK: IL-23 mediates inflammatory responses to mucoid Pseudomonas aeruginosa lung infection in mice. Am J Physiol Lung Cell Mol Physiol 2007,292(2):L519-L528.CrossRefPubMed Dubin PJ, Kolls JK: IL-23 mediates inflammatory responses to mucoid Pseudomonas aeruginosa lung infection in mice. Am J Physiol Lung Cell Mol Physiol 2007,292(2):L519-L528.CrossRefPubMed
22.
go back to reference Sagel SD, Gibson RL, Emerson J, McNamara S, Burns JL, Wagener JS, et al.: Impact of Pseudomonas and Staphylococcus infection on inflammation and clinical status in young children with cystic fibrosis. J Pediatr 2009,154(2):183–8.CrossRefPubMed Sagel SD, Gibson RL, Emerson J, McNamara S, Burns JL, Wagener JS, et al.: Impact of Pseudomonas and Staphylococcus infection on inflammation and clinical status in young children with cystic fibrosis. J Pediatr 2009,154(2):183–8.CrossRefPubMed
23.
go back to reference Bodini A, D'Orazio C, Peroni DG, Corradi M, Zerman L, Folesani G, et al.: IL-8 and pH values in exhaled condensate after antibiotics in cystic fibrosis children. Int J Immunopathol Pharmacol 2007,20(3):467–72.PubMed Bodini A, D'Orazio C, Peroni DG, Corradi M, Zerman L, Folesani G, et al.: IL-8 and pH values in exhaled condensate after antibiotics in cystic fibrosis children. Int J Immunopathol Pharmacol 2007,20(3):467–72.PubMed
24.
go back to reference Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, et al.: Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 1999,11(4):443–51.CrossRefPubMed Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, et al.: Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 1999,11(4):443–51.CrossRefPubMed
25.
go back to reference Konstan MW, Morgan WJ, Butler SM, Pasta DJ, Craib ML, Silva SJ, et al.: Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis. J Pediatr 2007,151(2):134–9. 139CrossRefPubMed Konstan MW, Morgan WJ, Butler SM, Pasta DJ, Craib ML, Silva SJ, et al.: Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis. J Pediatr 2007,151(2):134–9. 139CrossRefPubMed
26.
go back to reference Johansen HK, Nir M, Hoiby N, Koch C, Schwartz M: Severity of cystic fibrosis in patients homozygous and heterozygous for delta F508 mutation. Lancet 1991,337(8742):631–4.CrossRefPubMed Johansen HK, Nir M, Hoiby N, Koch C, Schwartz M: Severity of cystic fibrosis in patients homozygous and heterozygous for delta F508 mutation. Lancet 1991,337(8742):631–4.CrossRefPubMed
27.
go back to reference Hoshino H, Laan M, Sjostrand M, Lotvall J, Skoogh BE, Linden A: Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo. J Allergy Clin Immunol 2000,105(1 Pt 1):143–9.CrossRefPubMed Hoshino H, Laan M, Sjostrand M, Lotvall J, Skoogh BE, Linden A: Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo. J Allergy Clin Immunol 2000,105(1 Pt 1):143–9.CrossRefPubMed
28.
go back to reference Mackerness KJ, Jenkins GR, Bush A, Jose PJ: Characterisation of the range of neutrophil stimulating mediators in cystic fibrosis sputum. Thorax 2008,63(7):614–20.CrossRefPubMed Mackerness KJ, Jenkins GR, Bush A, Jose PJ: Characterisation of the range of neutrophil stimulating mediators in cystic fibrosis sputum. Thorax 2008,63(7):614–20.CrossRefPubMed
29.
go back to reference Lee KA, Kang MH, Lee YS, Kim YJ, Kim DH, Ko HJ, et al.: A distinct subset of natural killer T cells produces IL-17, contributing to airway infiltration of neutrophils but not to airway hyperreactivity. Cell Immunol 2008,251(1):50–5.CrossRefPubMed Lee KA, Kang MH, Lee YS, Kim YJ, Kim DH, Ko HJ, et al.: A distinct subset of natural killer T cells produces IL-17, contributing to airway infiltration of neutrophils but not to airway hyperreactivity. Cell Immunol 2008,251(1):50–5.CrossRefPubMed
30.
go back to reference Peng MY, Wang ZH, Yao CY, Jiang LN, Jin QL, Wang J, et al.: Interleukin 17-producing gamma delta T cells increased in patients with active pulmonary tuberculosis. Cell Mol Immunol 2008,5(3):203–8.CrossRefPubMedPubMedCentral Peng MY, Wang ZH, Yao CY, Jiang LN, Jin QL, Wang J, et al.: Interleukin 17-producing gamma delta T cells increased in patients with active pulmonary tuberculosis. Cell Mol Immunol 2008,5(3):203–8.CrossRefPubMedPubMedCentral
31.
go back to reference Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N, et al.: IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 2001,108(3):430–8.CrossRefPubMed Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N, et al.: IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 2001,108(3):430–8.CrossRefPubMed
32.
go back to reference Ferretti S, Bonneau O, Dubois GR, Jones CE, Trifilieff A: IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger. J Immunol 2003,170(4):2106–12.CrossRefPubMed Ferretti S, Bonneau O, Dubois GR, Jones CE, Trifilieff A: IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger. J Immunol 2003,170(4):2106–12.CrossRefPubMed
33.
go back to reference Song C, Luo L, Lei Z, Li B, Liang Z, Liu G, et al.: IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma. J Immunol 2008,181(9):6117–24.CrossRefPubMed Song C, Luo L, Lei Z, Li B, Liang Z, Liu G, et al.: IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma. J Immunol 2008,181(9):6117–24.CrossRefPubMed
Metadata
Title
Elevated expression of both mRNA and protein levels of IL-17A in sputum of stable Cystic Fibrosis patients
Authors
Ann Decraene
Anna Willems-Widyastuti
Ahmad Kasran
Kris De Boeck
Dominique M Bullens
Lieven J Dupont
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2010
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-11-177

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