Abstract
Background: The overexpression of interferon (IFN)γ or interleukin (IL)-13 in the adult murine lung induces the development of changes that mirror human lung emphysema.
Methods: IL-13 and IFNγ expression was determined in lung samples from five groups of patients: severe emphysema without α1-antitrypsin deficiency (SE+, n = 10); severe emphysema with α1-antitrypsin deficiency (SE–, n = 5); mild localised emphysema (ME, n = 8); non-emphysema smokers (NE-S, n = 9), and non-emphysema non-smokers (NE-NS, n = 11). Lung IL-13 and IFNγ mRNA were analysed by RT-PCR. Lung concentrations of IL-13 protein were assessed by ELISA.
Results: The expression of IFNγ mRNA was similar in patients with or without emphysema. IL-13 mRNA was markedly decreased in the SE+ group compared with the SE– (p = 0.04), ME (p = 0.02), and non-emphysema groups (p = 0.01). IL-13 mRNA correlated with forced expiratory volume in 1 second (r = 0.5, p = 0.04) and arterial oxygen tension (r = 0.45, p = 0.03) in emphysema patients. In contrast to the non-emphysematous lung, IL-13 protein was below the detection limit of the assay in most emphysematous lung homogenates.
Conclusion: The lung IL-13 content is reduced in patients with severe emphysema without α1-antitrypsin deficiency.
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- Barnes P. J. Chronic obstructive pulmonary disease. N Engl J Med. 2000 Jul 27;343(4):269–280. doi: 10.1056/NEJM200007273430407. [DOI] [PubMed] [Google Scholar]
- DeMeo D. L., Silverman E. K. Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. Thorax. 2004 Mar;59(3):259–264. doi: 10.1136/thx.2003.006502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diaz P. T., King M. A., Pacht E. R., Wewers M. D., Gadek J. E., Nagaraja H. N., Drake J., Clanton T. L. Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers. Ann Intern Med. 2000 Mar 7;132(5):369–372. doi: 10.7326/0003-4819-132-5-200003070-00006. [DOI] [PubMed] [Google Scholar]
- Erkinjuntti-Pekkanen R., Rytkonen H., Kokkarinen J. I., Tukiainen H. O., Partanen K., Terho E. O. Long-term risk of emphysema in patients with farmer's lung and matched control farmers. Am J Respir Crit Care Med. 1998 Aug;158(2):662–665. doi: 10.1164/ajrccm.158.2.9710012. [DOI] [PubMed] [Google Scholar]
- Finke J., Fritzen R., Ternes P., Lange W., Dölken G. An improved strategy and a useful housekeeping gene for RNA analysis from formalin-fixed, paraffin-embedded tissues by PCR. Biotechniques. 1993 Mar;14(3):448–453. [PubMed] [Google Scholar]
- Finkelstein R., Fraser R. S., Ghezzo H., Cosio M. G. Alveolar inflammation and its relation to emphysema in smokers. Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 1):1666–1672. doi: 10.1164/ajrccm.152.5.7582312. [DOI] [PubMed] [Google Scholar]
- Hancock A., Armstrong L., Gama R., Millar A. Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am J Respir Cell Mol Biol. 1998 Jan;18(1):60–65. doi: 10.1165/ajrcmb.18.1.2627. [DOI] [PubMed] [Google Scholar]
- He Jian-Qing, Connett John E., Anthonisen Nicholas R., Sandford Andrew J. Polymorphisms in the IL13, IL13RA1, and IL4RA genes and rate of decline in lung function in smokers. Am J Respir Cell Mol Biol. 2003 Mar;28(3):379–385. doi: 10.1165/rcmb.4885. [DOI] [PubMed] [Google Scholar]
- Hogg J. C., Senior R. M. Chronic obstructive pulmonary disease - part 2: pathology and biochemistry of emphysema. Thorax. 2002 Sep;57(9):830–834. doi: 10.1136/thorax.57.9.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jovanovic D., Pelletier J. P., Alaaeddine N., Mineau F., Geng C., Ranger P., Martel-Pelletier J. Effect of IL-13 on cytokines, cytokine receptors and inhibitors on human osteoarthritis synovium and synovial fibroblasts. Osteoarthritis Cartilage. 1998 Jan;6(1):40–49. doi: 10.1053/joca.1997.0091. [DOI] [PubMed] [Google Scholar]
- Kasahara Y., Tuder R. M., Cool C. D., Lynch D. A., Flores S. C., Voelkel N. F. Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med. 2001 Mar;163(3 Pt 1):737–744. doi: 10.1164/ajrccm.163.3.2002117. [DOI] [PubMed] [Google Scholar]
- Ke Bibo, Shen Xiu-Da, Zhai Yuan, Gao Feng, Busuttil Ronald W., Volk Hans-Dieter, Kupiec-Weglinski Jerzy W. Heme oxygenase 1 mediates the immunomodulatory and antiapoptotic effects of interleukin 13 gene therapy in vivo and in vitro. Hum Gene Ther. 2002 Oct 10;13(15):1845–1857. doi: 10.1089/104303402760372945. [DOI] [PubMed] [Google Scholar]
- Lanone Sophie, Zheng Tao, Zhu Zhou, Liu Wei, Lee Chun Geun, Ma Bing, Chen Qingsheng, Homer Robert J., Wang Jingming, Rabach Lesley A. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling. J Clin Invest. 2002 Aug;110(4):463–474. doi: 10.1172/JCI14136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee C. G., Homer R. J., Zhu Z., Lanone S., Wang X., Koteliansky V., Shipley J. M., Gotwals P., Noble P., Chen Q. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med. 2001 Sep 17;194(6):809–821. doi: 10.1084/jem.194.6.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lucey Edgar C., Keane Joseph, Kuang Ping-Ping, Snider Gordon L., Goldstein Ronald H. Severity of elastase-induced emphysema is decreased in tumor necrosis factor-alpha and interleukin-1beta receptor-deficient mice. Lab Invest. 2002 Jan;82(1):79–85. doi: 10.1038/labinvest.3780397. [DOI] [PubMed] [Google Scholar]
- Mahadeva R., Lomas D. A. Genetics and respiratory disease. 2. Alpha 1-antitrypsin deficiency, cirrhosis and emphysema. Thorax. 1998 Jun;53(6):501–505. doi: 10.1136/thx.53.6.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Majori M., Corradi M., Caminati A., Cacciani G., Bertacco S., Pesci A. Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):458–462. doi: 10.1016/s0091-6749(99)70471-9. [DOI] [PubMed] [Google Scholar]
- Morris David G., Huang Xiaozhu, Kaminski Naftali, Wang Yanli, Shapiro Steven D., Dolganov Gregory, Glick Adam, Sheppard Dean. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Nature. 2003 Mar 13;422(6928):169–173. doi: 10.1038/nature01413. [DOI] [PubMed] [Google Scholar]
- Neptune Enid R., Frischmeyer Pamela A., Arking Dan E., Myers Loretha, Bunton Tracie E., Gayraud Barbara, Ramirez Francesco, Sakai Lynn Y., Dietz Harry C. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet. 2003 Feb 24;33(3):407–411. doi: 10.1038/ng1116. [DOI] [PubMed] [Google Scholar]
- Retamales I., Elliott W. M., Meshi B., Coxson H. O., Pare P. D., Sciurba F. C., Rogers R. M., Hayashi S., Hogg J. C. Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am J Respir Crit Care Med. 2001 Aug 1;164(3):469–473. doi: 10.1164/ajrccm.164.3.2007149. [DOI] [PubMed] [Google Scholar]
- Segura-Valdez L., Pardo A., Gaxiola M., Uhal B. D., Becerril C., Selman M. Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest. 2000 Mar;117(3):684–694. doi: 10.1378/chest.117.3.684. [DOI] [PubMed] [Google Scholar]
- Shapiro S. D. The macrophage in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 2):S29–S32. doi: 10.1164/ajrccm.160.supplement_1.9. [DOI] [PubMed] [Google Scholar]
- Tardif G., Pelletier J. P., Dupuis M., Geng C., Cloutier J. M., Martel-Pelletier J. Collagenase 3 production by human osteoarthritic chondrocytes in response to growth factors and cytokines is a function of the physiologic state of the cells. Arthritis Rheum. 1999 Jun;42(6):1147–1158. doi: 10.1002/1529-0131(199906)42:6<1147::AID-ANR11>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
- Turato Graziella, Zuin Renzo, Miniati Massimo, Baraldo Simonetta, Rea Federico, Beghé Bianca, Monti Simonetta, Formichi Bruno, Boschetto Piera, Harari Sergio. Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema. Am J Respir Crit Care Med. 2002 Jul 1;166(1):105–110. doi: 10.1164/rccm.2111084. [DOI] [PubMed] [Google Scholar]
- Wang Z., Zheng T., Zhu Z., Homer R. J., Riese R. J., Chapman H. A., Jr, Shapiro S. D., Elias J. A. Interferon gamma induction of pulmonary emphysema in the adult murine lung. J Exp Med. 2000 Dec 4;192(11):1587–1600. doi: 10.1084/jem.192.11.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wynn Thomas A. IL-13 effector functions. Annu Rev Immunol. 2001 Dec 19;21:425–456. doi: 10.1146/annurev.immunol.21.120601.141142. [DOI] [PubMed] [Google Scholar]
- Zheng T., Zhu Z., Wang Z., Homer R. J., Ma B., Riese R. J., Jr, Chapman H. A., Jr, Shapiro S. D., Elias J. A. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest. 2000 Nov;106(9):1081–1093. doi: 10.1172/JCI10458. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Pouw Kraan T. C. T. M., Kükaycan M., Bakker A. M., Baggen J. M. C., van der Zee J. S., Dentener M. A., Wouters E. F. M., Verweij C. L. Chronic obstructive pulmonary disease is associated with the -1055 IL-13 promoter polymorphism. Genes Immun. 2002 Nov;3(7):436–439. doi: 10.1038/sj.gene.6363896. [DOI] [PubMed] [Google Scholar]