DOI: 10.1152/ajplung.1999.276.4.l596. Regulation of 15-lipoxygenase expression and mucus secretion by IL-4 in human bronchial epithelial cells

Regulation of 15-lipoxygenase expression and mucus secretion by IL-4 in human bronchial epithelial cells

10.1152/ajplung.1999.276.4.l596

Crossref journal-article

American Physiological Society

American Journal of Physiology-Lung Cellular and Molecular Physiology (24)

Abstract

Our laboratory has recently shown that mucus differentiation of cultured normal human tracheobronchial epithelial (NHTBE) cells is accompanied by the increased expression of 15-lipoxygenase (15-LO). We used differentiated NHTBE cells to investigate the regulation of 15-LO expression and mucus secretion by inflammatory cytokines. Interleukin (IL)-4 and IL-13 dramatically enhanced the expression of 15-LO, whereas tumor necrosis factor-α, IL-1β, and interferon (IFN)-γ had no effect. These cytokines did not increase the expression of cyclooxygenase-2, with the exception of a modest induction by IL-1β. The IL-4-induced 15-LO expression was concentration dependent, and mRNA and protein expression increased within 3 and 6 h, respectively, after IL-4 treatment. In metabolism studies with intact cells, 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) were the major metabolites formed from exogenous arachidonic acid and linoleic acid. No prostaglandins were detected. IL-4 treatment dramatically increased the formation of 13-HODE and 15-HETE compared with that in untreated NHTBE cells, and several additional 15-LO metabolites were observed. Pretreatment of NHTBE cells with IFN-γ or dexamethasone did not inhibit the IL-4-induced expression of 15-LO except at high concentrations (100 ng/ml of IFN-γ and 10 μM dexamethasone). IL-4 treatment inhibited mucus secretion and attenuated the expression of the mucin genes MUC5AC and MUC5B at 12–24 h after treatment. Addition of 15-HETE precursor and 13-HODE precursor to the cultures did not alter mucin secretion or mucin gene expression. On the basis of the data presented, we conclude that the increase in 15-LO expression by IL-4 and attenuation of mucus secretion may be independent biological events.

Bibliography

Jayawickreme, S. P., Gray, T., Nettesheim, P., & Eling, T. (1999). Regulation of 15-lipoxygenase expression and mucus secretion by IL-4 in human bronchial epithelial cells. American Journal of Physiology-Lung Cellular and Molecular Physiology, 276(4), L596âL603.

Authors 4

S. P. Jayawickreme (first)
T. Gray (additional)
P. Nettesheim (additional)
T. Eling (additional)

References 39 Referenced 25

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Dates

Type	When
Created	7 years, 8 months ago (Dec. 23, 2017, 5:44 p.m.)
Deposited	2 years ago (Aug. 30, 2023, 1:50 a.m.)
Indexed	5 months, 1 week ago (March 30, 2025, 8:27 a.m.)
Issued	26 years, 5 months ago (April 1, 1999)
Published	26 years, 5 months ago (April 1, 1999)
Published Print	26 years, 5 months ago (April 1, 1999)

Funders 0

None

BibTeX

@article{Jayawickreme_1999, title={Regulation of 15-lipoxygenase expression and mucus secretion by IL-4 in human bronchial epithelial cells}, volume={276}, ISSN={1522-1504}, url={http://dx.doi.org/10.1152/ajplung.1999.276.4.l596}, DOI={10.1152/ajplung.1999.276.4.l596}, number={4}, journal={American Journal of Physiology-Lung Cellular and Molecular Physiology}, publisher={American Physiological Society}, author={Jayawickreme, S. P. and Gray, T. and Nettesheim, P. and Eling, T.}, year={1999}, month=apr, pages={L596–L603} }

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  "abstract": "<jats:p>Our laboratory has recently shown that mucus differentiation of cultured normal human tracheobronchial epithelial (NHTBE) cells is accompanied by the increased expression of 15-lipoxygenase (15-LO). We used differentiated NHTBE cells to investigate the regulation of 15-LO expression and mucus secretion by inflammatory cytokines. Interleukin (IL)-4 and IL-13 dramatically enhanced the expression of 15-LO, whereas tumor necrosis factor-\u03b1, IL-1\u03b2, and interferon (IFN)-\u03b3 had no effect. These cytokines did not increase the expression of cyclooxygenase-2, with the exception of a modest induction by IL-1\u03b2. The IL-4-induced 15-LO expression was concentration dependent, and mRNA and protein expression increased within 3 and 6 h, respectively, after IL-4 treatment. In metabolism studies with intact cells, 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) were the major metabolites formed from exogenous arachidonic acid and linoleic acid. No prostaglandins were detected. IL-4 treatment dramatically increased the formation of 13-HODE and 15-HETE compared with that in untreated NHTBE cells, and several additional 15-LO metabolites were observed. Pretreatment of NHTBE cells with IFN-\u03b3 or dexamethasone did not inhibit the IL-4-induced expression of 15-LO except at high concentrations (100 ng/ml of IFN-\u03b3 and 10 \u03bcM dexamethasone). IL-4 treatment inhibited mucus secretion and attenuated the expression of the mucin genes MUC5AC and MUC5B at 12\u201324 h after treatment. Addition of 15-HETE precursor and 13-HODE precursor to the cultures did not alter mucin secretion or mucin gene expression. On the basis of the data presented, we conclude that the increase in 15-LO expression by IL-4 and attenuation of mucus secretion may be independent biological events.</jats:p>",
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