Inhibition of angiogenesis by IL-32: Possible role in asthma

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 4; pp. 964 - 973.e7
• Main Authors: Meyer, Norbert, MD, Christoph, Janine, MSc, Makrinioti, Heidi, MD, Indermitte, Philippe, Dipl Ing FH, Rhyner, Claudio, PhD, Soyka, Michael, MD, Eiwegger, Thomas, MD, Chalubinski, Maciej, MD, PhD, Wanke, Kerstin, MSc, Fujita, Hiroyuki, MD, PhD, Wawrzyniak, Paulina, MSc, Bürgler, Simone, PhD, Zhang, Sherrie, PhD, Akdis, Mübeccel, MD, PhD, Menz, Günter, MD, Akdis, Cezmi, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2012; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Airway management; Allergy and Immunology; Angiogenesis; Anti-Asthmatic Agents - therapeutic use; Asthma; Asthma - drug therapy; Asthma - genetics; Asthma - metabolism; Biological and medical sciences; Biopsy; Blood vessels; Bronchi - blood supply; Bronchial epithelial cells; Cell adhesion & migration; Cell Line; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; Cytokines; Endothelial cells; endotype; Enzyme-linked immunosorbent assay; Epithelial cells; Epithelial Cells - metabolism; Female; Flow cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gamma -Interferon; Gene Silencing; Helper cells; HIV; Human immunodeficiency virus; Humans; IL-32; Immune system; Immunopathology; Inflammation; Inflammatory diseases; Interferon-gamma - blood; Interleukins - genetics; Interleukins - metabolism; Ligands; Lymphocytes; Lymphocytes T; Male; Medical sciences; Middle Aged; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Picornaviridae Infections - immunology; Picornaviridae Infections - metabolism; Platelet-derived growth factor; Platelet-Derived Growth Factor - metabolism; Pneumology; Polymerase chain reaction; Respiratory Mucosa - metabolism; Respiratory tract; Respiratory tract diseases; Rhinovirus; RNA, Messenger - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Serum levels; siRNA; Smooth muscle; Sputum; Steroids; Toll-Like Receptors - metabolism; Transfection; Tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - blood; umbilical vein; Up-Regulation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Western blotting; Young Adult; Platelet-derived growth factor; Polyinosinic:polycytidylic acid; angiogenesis; VEGF; Eosinophilic cationic protein; Treg; poly[I:C]; Small interfering RNA; asthma; Human umbilical vein endothelial cell; siRNA; IL-32; Normal human bronchial epithelial; Bronchial epithelial cells; ECP; endotype; vascular endothelial growth factor; PDGF; Regulatory T; HUVEC; NHBE; TLR; Toll-like receptor; Lung disease; Immunopathology; Respiratory disease; Cytokine; Bronchus; Respiratory system; Asthma; Respiratory tract; Angiogenesis; Vascular endothelium growth factor; Immunology; Bronchus disease; Epithelial cell; Inhibitor; Obstructive pulmonary disease; Inhibition; Neovascularization
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2011.12.1002

Background IL-32 is a proinflammatory cytokine involved in various chronic inflammatory diseases. Chronic airway inflammation in asthmatic patients results in structural airway changes, including angiogenesis. Vascular endothelial growth factor (VEGF) is a key inducer of angiogenesis in the airways of asthmatic patients. Objective The aim of the study was to investigate the expression and function of IL-32 in patients with angiogenesis and asthma. Methods The expression and regulation of IL-32 in normal human bronchial epithelial (NHBE) cells was analyzed by using RT-PCR, ELISA, Western blotting, immunofluorescent staining, and flow cytometry. After knockdown of IL-32 in NHBE cells by small interfering RNA (siRNA) transfections, VEGF secretion was quantified by means of ELISA. New blood vessel formation was determined with human umbilical vein endothelial cells by culturing with supernatants from IL-32 siRNA–transfected NHBE cells. IL-32 was determined in serum and induced sputum samples of asthmatic patients and healthy control subjects by means of ELISA. Results IL-32 is expressed in NHBE cells on stimulation with IFN-γ, TNF-α, TH 1 cells, and rhinovirus. Inhibition of IL-32 expression resulted in significantly increased secretion of the proangiogenic factors VEGF and platelet-derived growth factor by NHBE cells. Human umbilical vein endothelial cells cultured in supernatants from IL-32 siRNA–transfected NHBE cells showed enhanced in vitro angiogenesis. IL-32 is detectable in induced sputum from asthmatic patients. IL-32 serum levels were significantly higher in asthmatic patients compared with those seen in healthy control subjects and correlated with response to asthma treatment. Conclusion IL-32 is induced by IFN-γ, TNF-α, TH 1 cells, and rhinovirus in bronchial epithelial cells. It inhibits angiogenesis, and its serum levels are associated with a good treatment response in asthmatic patients.