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Up‐regulation of production of TGF‐β and IL‐4 and down‐regulation of IL‐6 by apoptotic human bronchial epithelial cells
Author(s) -
Hodge Sandra,
Hodge Greg,
Flower Robert,
Reynolds Paul N,
Scicchitano Raffaele,
Holmes Mark
Publication year - 2002
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.2002.01120.x
Subject(s) - squamous metaplasia , apoptosis , autocrine signalling , cytokine , cancer research , inflammation , epithelium , interleukin , biology , immunology , cell culture , pathology , medicine , biochemistry , genetics
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‐β1 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‐β, 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‐β 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‐β and IL‐4 (but less IL‐6) than viable cells. Increased production of TGF‐β 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.