Regulation of 15-lipoxygenase isozymes and mucin secretion by cytokines in cultured normal human bronchial epithelial cells.
OBJECTIVE
To study the effects of IL-4, IL-13, IL-1beta, IL-8 and TNFalpha on 15-lipoxygenase(15-LO) isozyme expression and mucin secretion in normal human bronchial epithelial cells.


METHODS
The effects of IL-4, IL-13, IL-1beta, IL-8 and TNFalpha on 15-LO isoenzyme mRNA and protein expression, total 15-LO enzyme activity and mucin secretion were examined in cultures of normal human bronchial epithelial cells. In addition, in order to determine whether the observed effects on mucin secretion were due to lipoxygenase (LO) products, the effect of the non-selective LO inhibitor nordihydroguaiaretic acid was examined.


RESULTS
IL-4 and IL- 13 selectively enhanced 15-LOa mRNA and protein levels, and total 15-LO enzyme activity. In contrast, no changes were observed in 15-LOb mRNA or protein levels. IL-4 and IL-13 both reduced mucin secretion in this cell type, however the non-selective LO inhibitor nordihydroguaiaretic acid had no effect on this action of IL-4.


CONCLUSIONS
These data demonstrate that IL-4 and IL-13 selectively regulate the expression of the 15-LOa isozyme. However, 15LOa products do not mediate the IL-4-induced reduction in mucin secretion observed in this cell type.
Brown
C D
CD
Discovery Biology, Pfizer Global Research and Development, Sandwich, Kent, UK.
Kilty
I
I
Yeadon
M
M
Jenkinson
S
S
D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis / Q000235:genetics*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics*; D009077:Mucins / Q000378:metabolism*
D018793:Interleukin-13; D007527:Isoenzymes; D009077:Mucins; D015847:Interleukin-4; D001093:Arachidonate 15-Lipoxygenase