Interleukin-4 and tumour necrosis factor-alpha inhibit transforming growth factor-beta production in a human bronchial epithelial cell line: possible relevance to inflammatory mechanisms in chronic obstructive pulmonary disease.
OBJECTIVE
Human bronchial epithelial cells are known to secrete an array of inflammatory cytokines including tumour necrosis factor-alpha (TNF-alpha) 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-beta (TGF-beta) is an anti-inflammatory cytokine and is involved in airway repair. The purpose of this study was to study the effect of TNF-alpha and IL-4 (pro-inflammatory cytokines known to be up-regulated in COPD), on the production of TGF-beta (a negative regulator of inflammation) by epithelial cells.


METHODS
A bronchial epithelial cell line was used as an in vitro culture model (16HBE). Cell cultures were stimulated with various combinations of TNF-alpha and IL-4 (20 ng/mL) for 24 h. Transforming growth factor-beta production was measured by flow cytometry, enzyme-linked immunosorbent assay and immunohistochemistry.


RESULTS
Exposure to TNF-alpha significantly up-regulated production of IL-4 from cultured epithelial cells. Unstimulated cells spontaneously released TGF-beta. Exposure to TNF-alpha and IL-4 significantly inhibited production of TGF-beta. The inhibitory effects of TNF-alpha and IL-4 on TGF-beta synthesis were summative.


CONCLUSIONS
The inhibitory effect of IL-4 and TNF-alpha on production of the regulatory cytokine TGF-beta 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.
Hodge
S
S
Department of Thoracic Medicine, Royal Adelaide Hospital, North Terrrace, South Australia, Australia. sandy.hodge@imvs.sa.gov.au
Hodge
G
G
Holmes
M
M
Flower
R
R
Scicchitano
R
R
D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015847:Interleukin-4 / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4