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Interleukin‐4 and tumour necrosis factor‐ α inhibit transforming growth factor‐ β production in a human bronchial epithelial cell line: Possible relevance to inflammatory mechanisms in chronic obstructive pulmonary disease
Author(s) -
Hodge Sandra,
Hodge Greg,
Holmes Mark,
Flower Robert,
Scicchitano Raffaele
Publication year - 2001
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1046/j.1440-1843.2001.00335.x
Subject(s) - cytokine , medicine , tumor necrosis factor alpha , immunology , transforming growth factor beta , transforming growth factor , inflammation , interleukin , cancer research
Objective: Human bronchial epithelial cells are known to secrete an array of inflammatory cytokines including tumour necrosis factor‐α (TNF‐α) and interleukin (IL)‐4, which may play a role in immune responses in lung diseases such as chronic obstructive pulmonary disease (COPD). However, the regulatory mechanisms governing cytokine production in bronchial epithelia in COPD are largely unknown. Transforming growth factor‐β (TGF‐β) is an anti‐inflammatory cytokine and is involved in airway repair. The purpose of this study was to study the effect of TNF‐α and IL‐4 (pro‐inflammatory cytokines known to be up‐regulated in COPD), on the production of TGF‐β (a negative regulator of inflammation) by epithelial cells. Methodology: A bronchial epithelial cell line was used as an in vitro culture model (16HBE). Cell cultures were stimulated with various combinations of TNF‐α and IL‐4 (20 ng/mL) for 24 h. Transforming growth factor‐β production was measured by flow cytometry, enzyme‐linked immunosorbent assay and immunohistochemistry. Results: Exposure to TNF‐α significantly up‐regulated production of IL‐4 from cultured epithelial cells. Unstimulated cells spontaneously released TGF‐β. Exposure to TNF‐α and IL‐4 significantly inhibited production of TGF‐β. The inhibitory effects of TNF‐α and IL‐4 on TGF‐β synthesis were summative. Conclusions: The inhibitory effect of IL‐4 and TNF‐α on production of the regulatory cytokine TGF‐β in a bronchial epithelial cell line suggests that such mechanisms may contribute to the progression of the inflammatory response and compromise repair processes in inflammatory lung diseases such as COPD.