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

详细信息    查看全文

• 作者：Norbert Meyer ; MD^a ; ^b ; ^{norbert.meyer@siaf.uzh.ch} ; Janine Christoph ; MSc^b ; Heidi Makrinioti ; MD^a ; Philippe Indermitte ; Dipl Ing FH^a ; Claudio Rhyner ; PhD^a ; Michael Soyka ; MD^a ; Thomas Eiwegger ; MD^a ; ^c ; Maciej Chalubinski ; MD ; PhD^a ; Kerstin Wanke ; MSc^a ; Hiroyuki Fujita ; MD ; PhD^a ; Paulina Wawrzyniak ; MSc^a ; Simone Bü ; rgler ; PhD^a ; Sherrie Zhang ; PhD^d ; Mü ; beccel Akdis ; MD ; PhD^a ; Gü ; nter Menz ; MD^b ; Cezmi Akdis ; MD^a ; ^{akdisac@siaf.uzh.ch}
• 关键词：Bronchial epithelial cells ; asthma ; IL-32 ; angiogenesis ; vascular endothelial growth factor ; endotype
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：April, 2012
• 年：2012
• 卷：129
• 期：4
• 页码：964-973.e7
• 全文大小：1077 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

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-¦Ã, TNF-¦Á, T_H1 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-¦Ã, TNF-¦Á, T_H1 cells, and rhinovirus in bronchial epithelial cells. It inhibits angiogenesis, and its serum levels are associated with a good treatment response in asthmatic patients.