Decreased expression of interleukin 13 in human lung emphysema

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.

[1]  E. Silverman,et al.  α1-Antitrypsin deficiency · 2: Genetic aspects of α1-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk , 2004, Thorax.

[2]  E. Silverman,et al.  Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. , 2004, Thorax.

[3]  T. Wynn.  IL-13 effector functions. , 2003, Annual review of immunology.

[4]  N. Kaminski,et al.  Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema , 2003, Nature.

[5]  N. Anthonisen,et al.  Polymorphisms in the IL13, IL13RA1, and IL4RA genes and rate of decline in lung function in smokers. , 2003, American journal of respiratory cell and molecular biology.

[6]  D. Arking,et al.  Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome , 2003, Nature Genetics.

[7]  N. Kaminski,et al.  Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. , 2003, Nature.

[8]  D. Arking,et al.  Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. , 2003, Nature genetics.

[9]  F. Gao,et al.  Heme oxygenase 1 mediates the immunomodulatory and antiapoptotic effects of interleukin 13 gene therapy in vivo and in vitro. , 2002, Human gene therapy.

[10]  J. Hogg,et al.  Chronic obstructive pulmonary disease c 2: Pathology and biochemistry of emphysema , 2002, Thorax.

[11]  B. Ma,et al.  Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling. , 2002, The Journal of clinical investigation.

[12]  B. Beghé,et al.  Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema. , 2002, American journal of respiratory and critical care medicine.

[13]  J. D’Armiento,et al.  Differential gene expression of sFRP-1 and apoptosis in pulmonary emphysema. , 2002, Chest.

[14]  D. Postma,et al.  Chronic obstructive pulmonary disease. , 2002, Clinical evidence.

[15]  J. Keane,et al.  Severity of elastase-induced emphysema is decreased in tumor necrosis factor-alpha and interleukin-1beta receptor-deficient mice. , 2002, Laboratory investigation; a journal of technical methods and pathology.

[16]  E. Wouters,et al.  Chronic obstructive pulmonary disease is associated with the -1055 IL-13 promoter polymorphism , 2002, Genes and Immunity.

[17]  J. Keane,et al.  Severity of Elastase-Induced Emphysema Is Decreased in Tumor Necrosis Factor-α and Interleukin-1β Receptor-Deficient Mice , 2002, Laboratory Investigation.

[18]  R. Homer,et al.  Interleukin-13 Induces Tissue Fibrosis by Selectively Stimulating and Activating Transforming Growth Factor β1 , 2001, The Journal of experimental medicine.

[19]  P. Paré,et al.  Amplification of inflammation in emphysema and its association with latent adenoviral infection. , 2001, American journal of respiratory and critical care medicine.

[20]  D A Lynch,et al.  Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. , 2001, American journal of respiratory and critical care medicine.

[21]  M. Fujita,et al.  Overexpression of tumor necrosis factor-alpha produces an increase in lung volumes and pulmonary hypertension. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[22]  R. Homer,et al.  Interferon γ Induction of Pulmonary Emphysema in the Adult Murine Lung , 2000, The Journal of experimental medicine.

[23]  B. Ma,et al.  Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. , 2000, The Journal of clinical investigation.

[24]  H. Nagaraja,et al.  Increased Susceptibility to Pulmonary Emphysema among HIV-Seropositive Smokers , 2000, Annals of Internal Medicine.

[25]  M. Gaxiola,et al.  Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. , 2000, Chest.

[26]  S. Shapiro,et al.  The macrophage in chronic obstructive pulmonary disease. , 1999, American journal of respiratory and critical care medicine.

[27]  J. Pelletier,et al.  Collagenase 3 production by human osteoarthritic chondrocytes in response to growth factors and cytokines is a function of the physiologic state of the cells. , 1999, Arthritis and rheumatism.

[28]  M. Corradi,et al.  Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease. , 1999, The Journal of allergy and clinical immunology.

[29]  K. Partanen,et al.  Long-term risk of emphysema in patients with farmer's lung and matched control farmers. , 1998, American journal of respiratory and critical care medicine.

[30]  D. Lomas,et al.  Alpha1-antitrypsin deficiency, cirrhosis and emphysema , 1998 .

[31]  D. Lomas,et al.  Genetics and respiratory disease. 2. Alpha 1-antitrypsin deficiency, cirrhosis and emphysema. , 1998, Thorax.

[32]  J. Pelletier,et al.  Effect of IL-13 on cytokines, cytokine receptors and inhibitors on human osteoarthritis synovium and synovial fibroblasts. , 1998, Osteoarthritis and cartilage.

[33]  L. Armstrong,et al.  Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. , 1998, American journal of respiratory cell and molecular biology.

[34]  M. Cosio,et al.  Alveolar inflammation and its relation to emphysema in smokers. , 1995, American journal of respiratory and critical care medicine.

[35]  P. Ternes,et al.  An improved strategy and a useful housekeeping gene for RNA analysis from formalin-fixed, paraffin-embedded tissues by PCR. , 1993, BioTechniques.