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Type: Journal article
Title: Up-regulation of production of TGF-β and IL-4 and down-regulation of IL-6 by apoptotic human bronchial epithelial cells
Other Titles: Up-regulation of production of TGF-beta and IL-4 and down-regulation of IL-6 by apoptotic human bronchial epithelial cells
Author: Hodge, S.
Hodge, G.
Flower, R.
Reynolds, P.
Scicchitano, R.
Holmes, M.
Citation: Immunology and Cell Biology, 2002; 80(6):537-543
Publisher: Blackwell Science Asia
Issue Date: 2002
ISSN: 0818-9641
Statement of
Sandra Hodge ; Greg Hodge ; Robert Flower ; Paul N Reynolds ; Raffaele Scicchitano ; Mark Holmes
Abstract: Human bronchial epithelial cells secrete cytokines that play a role in immune responses in the lung. However, the roles of these cytokines in regulating epithelial repair following acute lung injury are largely unknown. Responses to injury include hyperplasia of epithelial cells and squamous metaplasia. The resolution stage is characterized by discontinuation of hyperplasia. Apoptosis is considered to be the most efficient mechanism of removal of unwanted cells without causing inflammation. The presence of TGF-beta1 increases apoptosis, induces squamous metaplasia and inhibits proliferation of airway epithelial cells. Interleukin-4 increases the ability of macrophages to phagocytose epithelial cells and produce inflammatory cytokines. The purpose of this study was to investigate the hypothesis that apoptotic lung epithelial cells produce cytokines, which could act in an autocrine manner to control hyperplasia and induce squamous differentiation following acute lung injury. A bronchial epithelial cell line (16 HBE) was used as an in vitro model, to study the production of TGF-beta, IL-4 and IL-6 by lung epithelial cells undergoing apoptosis. Apoptotic and live cells were sorted on the basis of bright and negative staining with FITC-conjugated Annexin V, respectively. Intracellular IL-6, TGF-beta and IL-4 was measured using flow cytometric techniques. Electron microscopy, immunohistochemistry and ELISA were used as supportive techniques. Apoptotic cells produced significantly more TGF-beta and IL-4 (but less IL-6) than viable cells. Increased production of TGF-beta and IL-4 by epithelial cells undergoing apoptosis may contribute to the inhibition of proliferation, squamous metaplasia, and reduction of the inflammatory response in acute lung injury.
Keywords: Apoptosis
flow cytometry
lung epithelial cell
DOI: 10.1046/j.1440-1711.2002.01120.x
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