Partial divergence of cytokine mRNA expression in bronchial tissues compared to bronchoalveolar lavage cells in horses with recurrent airway obstruction.
Riihimaki, M.; Raine, Amanda; Art, Tatianaet al.
2008 • In Veterinary Immunology and Immunopathology, 122 (3-4), p. 256-64
[en] The aim of this study was to investigate mRNA levels of cytokines in bronchial epithelium in horses with recurrent airway obstruction (RAO) during acute crisis and remission. Additionally, cytokine mRNA levels in endobronchial biopsies and bronchoalveolar lavage (BAL) cells were compared. Seven RAO horses were examined while in respiratory crisis following provocation and again while in remission after 2 months on pasture, during which time six healthy horses on pasture were also examined. Quantitative real-time PCR (RT-PCR) was used to assess mRNA expression for cytokines IL-5, IL-6, IL-8, IL-10, IL-17 and transforming growth factor beta1 (TGF-beta1) in endobronchial biopsies and bronchoalveolar lavage. Expression of IL-8 mRNA was significantly upregulated during crisis in both endobronchial biopsies and BAL cells (p=0.036), while there was a similar trend for upregulation of IL-10 mRNA only in BAL cells that approached significance (p=0.059). Moreover, during crisis the expression of IL-8 mRNA in BAL cells was positively correlated to relative IL-6 mRNA expression (r(s)=0.971, p=0.001) and bronchial epithelial expression of IL-10 and TGF-beta1 mRNA were positively correlated (r(s)=0.943, p=0.005). In comparing the relationship of mRNA expression in BAL to biopsy in individual RAO horses, there was a positive correlation with IL-6 to IL-8 mRNA expression in BAL during respiratory crisis (r(s)=0.971, p=0.001) that also correlated positively with IL-8 expression in biopsies on pasture (r(s)=0.986, p<0.0001 for both). Regarding RAO horses at pasture versus controls neither the cytokine mRNA levels in endobronchial biopsy nor in BAL cells differed significantly. These results further support previous findings that IL-8 mRNA in both BAL cells and bronchial epithelium is upregulated in RAO horses during crisis. However, apart from IL-8, it appears that expression of other cytokines, including IL-5, IL-6, IL-10, IL-17 and TGF-beta1 in bronchial epithelium does not necessarily mirror cytokine expression in BAL cells in individual horses with RAO. Accordingly, examination of markers of inflammation in endobronchial tissue provides complementary but not necessarily identical information to that obtained in BAL cells. Given the potential for repeated sampling over time bronchial biopsy can serve as an invaluable additional tool for investigation of time-dependent changes in inflammatory process in this animal model of asthma.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Riihimaki, M.
Raine, Amanda
Art, Tatiana ; Université de Liège - ULiège > Département de sciences fonctionnelles > Phys. neuro-muscul., de l'effort - Méd. sport. des animaux
Lekeux, Pierre ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie - Doyen de la Faculté de Médecine vétérinaire
Couetil, L.
Pringle, J.
Language :
English
Title :
Partial divergence of cytokine mRNA expression in bronchial tissues compared to bronchoalveolar lavage cells in horses with recurrent airway obstruction.
Ainsworth, D.M., Grunig, G., Matychak, M.B., Young, J., Wagner, B., Erb, H.N., Antczak, D.F., Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells (2003) Vet. Immunol. Immunopathol., 96, pp. 83-91
Ainsworth, D.M., Wagner, B., Franchini, M., Grunig, G., Erb, H.N., Tan, J.Y., Time-dependent alterations in gene expression of interleukin-8 in the bronchial epithelium of horses with recurrent airway obstruction (2006) Am. J. Vet. Res., 67, pp. 669-677
Art, T., Franck, T., Lekeux, P., de Moffarts, B., Couetil, L., Becker, M., Kohnen, S., Serteyn, D., Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses and those with recurrent airway obstruction (2006) Can. J. Vet. Res., 70, pp. 291-296
Behndig, A.F., Mudway, I.S., Brown, J.L., Stenfors, N., Helleday, R., Duggan, S.T., Wilson, S.J., Blomberg, A., Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans (2006) Eur. Respir. J., 27, pp. 359-365
Berndt, A., Derksen, F.J., Venta, P.J., Ewart, S., Yuzbasiyan-Gurkan, V., Robinson, N.E., Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction (2007) Am. J. Physiol., 292, pp. L936-L943
Bureau, F., Bonizzi, G., Kirschvink, N., Delhalle, S., Desmecht, D., Merville, M.P., Bours, V., Lekeux, P., Correlation between nuclear factor-kappaB activity in bronchial brushing samples and lung dysfunction in an animal model of asthma (2000) Am. J. Respir. Crit. Care Med., 161, pp. 1314-1321
Bureau, F., Delhalle, S., Bonizzi, G., Fievez, L., Dogne, S., Kirschvink, N., Vanderplasschen, A., Lekeux, P., Mechanisms of persistent NF-kappa B activity in the bronchi of an animal model of asthma (2000) J. Immunol., 165, pp. 5822-5830
Couetil, L.L., Art, T., de Moffarts, B., Becker, M., Melotte, D., Jaspar, F., Bureau, F., Lekeux, P., DNA binding activity of transcription factors in bronchial cells of horses with recurrent airway obstruction (2006) Vet. Immunol. Immunopathol., 113, pp. 11-20
Davidson, A.J., Cytokine mRNA expression pattern in horses with large intestinal disease (2002) Res. Vet. Sci., 72, pp. 177-185
Davis, M.S., Malayer, J.R., Vandeventer, L., Royer, C.M., McKenzie, E.C., Williamson, K.K., Cold weather exercise and airway cytokine expression (2005) J. Appl. Physiol., 98, pp. 2132-2136
Davis, M.S., Williams, C.C., Meinkoth, J.H., Malayer, J.R., Royer, C.M., Williamson, K.K., McKenzie, E.C., Influx of neutrophils and persistence of cytokine expression in airways of horses after performing exercise while breathing cold air (2007) Am. J. Vet. Res., 68, pp. 185-189
Debrue, M., Hamilton, E., Joubert, P., Lajoie-Kadoch, S., Lavoie, J.P., Chronic exacerbation of equine heaves is associated with an increased expression of interleukin-17 mRNA in bronchoalveolar lavage cells (2005) Vet. Immunol. Immunopathol., 105, pp. 25-31
Desjardins, I., Theoret, C., Joubert, P., Wagner, B., Lavoie, J.P., Comparison of TGF-beta 1 concentrations in bronchoalveolar fluid of horses affected with heaves and of normal controls (2004) Vet. Immunol. Immunopathol., 101, pp. 133-141
Djukanovic, R., Roche, W.R., Wilson, J.W., Beasley, C.R., Twentyman, O.P., Howarth, R.H., Holgate, S.T., Mucosal inflammation in asthma (1990) Am. Rev. Respir. Dis., 142, pp. 434-457
Franchini, M., Gill, U., von Fellenberg, R., Bracher, V.D., Interleukin-8 concentration and neutrophil chemotactic activity in bronchoalveolar lavage fluid of horses with chronic obstructive pulmonary disease following exposure to hay (2000) Am. J. Vet. Res., 61, pp. 1369-1374
Franchini, M., Gilli, U., Akens, M.K., Fellenberg, R.V., Bracher, V., The role of neutrophil chemotactic cytokines in the pathogenesis of equine chronic obstructive pulmonary disease (COPD) (1998) Vet. Immunol. Immunopathol., 66, pp. 53-65
Fueki, N., Sagara, H., Akimoto, K., Ota, M., Okada, T., Sugiyama, K., Fueki, M., Fukuda, T., Interleukin-10 regulates transforming growth factor-beta signaling in cultured human bronchial epithelial cells (2007) Respiration
Int. Rev. Thorac. Dis., 74, pp. 454-459
Gamble, E., Qiu, Y., Wang, D., Zhu, J., Vignola, A.M., Kroegel, C., Morell, F., Jeffery, P.K., Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design (2006) Eur. Respir. J., 27, pp. 293-299
Gerber, V., Robinson, N.E., Venta, R.J., Rawson, J., Jefcoat, A.M., Hotchkiss, J.A., Mucin genes in horse airways: MUC5AC, but not MUC2, may play a role in recurrent airway obstruction (2003) Equine Vet. J., 35, pp. 252-257
Giguere, S., Viel, L., Lee, E., MacKay, R.J., Hernandez, J., Franchini, M., Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate (2002) Vet. Immunol. Immunopathol., 85, pp. 147-158
Hirota, J.A., Ellis, R., Inman, M.D., Regional differences in the pattern of airway remodeling following chronic allergen exposure in mice (2006) Respir. Res., 7, p. 120
Holgate, S.T., Inflammatory and structural changes in the airways of patients with asthma (2000) Respir Med, 94 (SUPPL. D), pp. S3-S6
Jeffery, P., Structural alterations and inflammation of bronchi in asthma (1998) Int. J. Clin. Pract. Suppl., 96, pp. 5-14
Jeffery, P., Holgate, S., Wenzel, S., Methods for the assessment of endobronchial biopsies in clinical research: application to studies of pathogenesis and the effects of treatment (2003) Am. J. Respir. Crit. Care Med., 168, pp. S1-S17
Jeffery, P.K., Bronchial biopsies and airway inflammation (1996) Eur. Respir. J., 9, pp. 1583-1587
Jeffery, P.K., Laitinen, A., Venge, P., Biopsy markers of airway inflammation and remodelling (2000) Respir. Med., 94 (SUPPL. F), pp. S9-S15
Jones, C.E., Chan, K., Interleukin-17 stimulates the expression of interleukin-8, growth-related oncogene-alpha, and granulocyte-colony-stimulating factor by human airway epithelial cells (2002) Am. J. Respir. Cell Mol. Biol., 26, pp. 748-753
Jovanovic, D.V., Di Battista, J.A., Martel-Pelletier, J., Jolicoeur, F.C., He, Y., Zhang, M., Mineau, F., Pelletier, J.P., IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages (1998) J. Immunol., 160, pp. 3513-3521
Knight, D.A., Holgate, S.T., The airway epithelium: structural and functional properties in health and disease (2003) Respirology, 8, pp. 432-446
Laan, T.T., Bull, S., Pirie, R., Fink-Gremmels, J., The role of alveolar macrophages in the pathogenesis of recurrent airway obstruction in horses (2006) J. Vet. Intern. Med., 20, pp. 167-174
Laan, T.T., Bull, S., Pirie, R.S., Fink-Gremmels, J., Evaluation of cytokine production by equine alveolar macrophages exposed to lipopolysaccharide, Aspergillus fumigatus, and a suspension of hay dust (2005) Am. J. Vet. Res., 66, pp. 1584-1589
Laan, T.T., Bull, S., van Nieuwstadt, R.A., Fink-Gremmels, J., The effect of aerosolized and intravenously administered clenbuterol and aerosolized fluticasone propionate on horses challenged with Aspergillus fumigatus antigen (2006) Vet. Res. Commun., 30, pp. 623-635
Linden, A., Adachi, M., Neutrophilic airway inflammation and IL-17 (2002) Allergy, 57, pp. 769-775
Linden, A., Hoshino, H., Laan, M., Airway neutrophils and interleukin-17 (2000) Eur. Respir. J., 15, pp. 973-977
Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method (2001) Methods, 25, pp. 402-408
Lugo, J., Harkema, J.R., deFeijter-Rupp, H., Bartner, L., Boruta, D., Robinson, N.E., Airway inflammation is associated with mucous cell metaplasia and increased intraepithelial stored mucosubstances in horses (2006) Vet. J., 172, pp. 293-301
Morris, D.D., Crowe, N., Moore, J.N., Moldawer, L.L., Endotoxin-induced production of interleukin 6 by equine peritoneal macrophages in vitro (1992) Am. J. Vet. Res., 53, pp. 1298-1301
Nakao, A., Miike, S., Hatano, M., Okumura, K., Tokuhisa, T., Ra, C., Iwamoto, I., Blockade of transforming growth factor beta/Smad signaling in T cells by overexpression of Smad7 enhances antigen-induced airway inflammation and airway reactivity (2000) J. Exp. Med., 192, pp. 151-158
Nakao, A., Sagara, H., Setoguchi, Y., Okada, T., Okumura, K., Ogawa, H., Fukuda, T., Expression of Smad7 in bronchial epithelial cells is inversely correlated to basement membrane thickness and airway hyperresponsiveness in patients with asthma (2002) J. Allergy Clin. Immunol., 110, pp. 873-878
Pirie, R.S., Collie, D.D., Dixon, P.M., McGorum, B.C., Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 2: Effects of inhaled HDS on control and heaves horses. (2002) Equine Vet. J., 34, pp. 337-342
Pirie, R.S., Dixon, P.M., McGorum, B.C., Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 3: Effect of fractionation of HDS (2002) Equine Vet. J., 34, pp. 343-347
Pirie, R.S., McLachlan, G., McGorum, B.C., Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 1: Preparation and composition of HDS (2002) Equine Vet. J., 34, pp. 332-336
Rennard, S.I., Romberger, D.J., Robbins, R.A., Spurzem, J.R., Is asthma an epithelial disease? (1995) Chest, 107, pp. 127S-131S
Riihimäki, M., Lilliehöök, I., Raine, A., Berg, M., Pringle, J., 2007. Clinical alterations and mRNA levels of IL-4 and IL-5 in bronchoalveolar cells of horses with transient pulmonary eosinophilia. Res. Vet. Sci., doi:10.1016/j.rvsc.2007.09.015
Robinson, N.E., International Workshop on Equine Chronic Airway Disease Michigan State University 16-18 June 2000 (2001) Equine Vet. J., 33, pp. 5-19
Rush, B.R., Raub, E.S., Rhoads, W.S., Flaminio, M.J., Matson, C.J., Hakala, J.E., Gillespie, J.R., Pulmonary function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively (1998) Am. J. Vet. Res., 59, pp. 1039-1043
Saetta, M., Jeffery, P.K., Maestrelli, P., Timens, W., Biopsies: processing and assessment (1998) Eur. Respir. J. Suppl., 26, pp. 20S-25S
Sagara, H., Okada, T., Okumura, K., Ogawa, H., Ra, C., Fukuda, T., Nakao, A., Activation of TGF-beta/Smad2 signaling is associated with airway remodeling in asthma (2002) J. Allergy Clin. Immunol., 110, pp. 249-254
Sandersen, C., Bureau, F., Turlej, R., Fievez, L., Dogne, S., Kirschvink, N., Lekeux, P., p65 Homodimer activity in distal airway cells determines lung dysfunction in equine heaves (2001) Vet. Immunol. Immunopathol., 80, pp. 315-326
Schatzmann, U., Straub, R., Gerber, H., Pauli, B., Percutaneous lung biopsy in the horse (1974) Vet. Rec., 94, pp. 588-590
Takizawa, H., Airway epithelial cells as regulators of airway inflammation (Review) (1998) Int. J. Mol. Med., 1, pp. 367-378
van den Hoven, R., Duvigneau, J.C., Hartl, R.T., Gemeiner, M., Clenbuterol affects the expression of messenger RNA for interleukin 10 in peripheral leukocytes from horses challenged intrabronchially with lipopolysaccharides (2006) Vet. Res. Commun., 30, pp. 921-928
Wyse, C.A., Skeldon, K., Hotchkiss, J.W., Gibson, G., Yam, P.S., Christley, R.M., Preston, T., Love, S., Effects of changes to the stable environment on the exhalation of ethane, carbon monoxide and hydrogen peroxide by horses with respiratory inflammation (2005) Vet. Rec., 157, pp. 408-412
Xing, Z., Gauldie, J., Cox, G., Baumann, H., Jordana, M., Lei, X.F., Achong, M.K., IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses (1998) J. Clin. Invest., 101, pp. 311-320
