Pro-inflammatory cytokines induce c-fos expression followed by IL-6 release in human airway smooth muscle cells.
BACKGROUND
Airway smooth muscle (ASM) is considered to be a target for mediators released during airway inflammation.


OBJECTIVE
To investigate the expression of c-fos, a constituent of the transcription factor activator protein-1, in human ASM cells. In addition, to measure the release of interleukin (IL)-6 into the conditioned medium of stimulated ASM cells, as well as DNA biosynthesis and changes in cell number.


METHODS
Serum-deprived human ASM cells in the G0/G1 phase were stimulated with the pro-inflammatory cytokines; tumour necrosis factor-alpha, IL-1beta, IL-5 and IL-6. The expression of mRNA encoding the proto-oncogene c-fos was measured by Northern blot analysis. Cell proliferation was assessed by [3H]-thymidine incorporation assays and cell counting, and IL-6 levels in cell-conditioned medium were measured by enzyme-linked immunosorbent assay.


RESULTS
All of the cytokines investigated induced a rapid (within 1 h) and transient increase in the expression of mRNA encoding c-fos, followed by the expression and enhanced release of IL-6. Cell proliferation remained unchanged in cytokine-stimulated cells.


CONCLUSIONS
Cytokine-induced c-fos expression in human ASM cells could be described as a marker of cell 'activation'. The possible association of these results with airway inflammation, through secondary intracellular mechanisms such as cytokine production, is discussed.
McKay
S
S
Department of Pharmacology, Erasmus University Medical Center, GE Rotterdam, The Netherlands.
Bromhaar
M M
MM
de Jongste
J C
JC
Hoogsteden
H C
HC
Saxena
P R
PR
Sharma
H S
HS
D001980:Bronchi / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology* / Q000494:pharmacology; D015848:Interleukin-5 / Q000276:immunology* / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology*; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D011519:Proto-Oncogenes; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D015848:Interleukin-5; D015850:Interleukin-6; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D013936:Thymidine