Skip to main content
Immunology logoLink to Immunology
. 1994 Mar;81(3):389–394.

Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells.

O J Kwon 1, B T Au 1, P D Collins 1, J N Baraniuk 1, I M Adcock 1, K F Chung 1, P J Barnes 1
PMCID: PMC1422337  PMID: 8206512

Abstract

Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in many cell types, including human airway epithelial cells (HAEC). Inhaled corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained from transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL-8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose-dependently in both resting and stimulated HAEC. The half-life of IL-8 mRNA determined in the presence of actinomycin D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play an important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their anti-inflammatory effects by blocking IL-8 gene expression and generation in these cells.

Full text

PDF
389

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Becker S., Quay J., Soukup J. Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages. J Immunol. 1991 Dec 15;147(12):4307–4312. [PubMed] [Google Scholar]
  2. Burnstein K. L., Cidlowski J. A. Regulation of gene expression by glucocorticoids. Annu Rev Physiol. 1989;51:683–699. doi: 10.1146/annurev.ph.51.030189.003343. [DOI] [PubMed] [Google Scholar]
  3. Cassatella M. A., Aste M., Calzetti F., Constantin G., Guasparri I., Ceska M., Rossi F. Studies on the regulatory mechanisms of interleukin-8 gene expression in resting and IFN-gamma-treated neutrophils: evidence on the capability of staurosporine of inducing the production of interleukin-8 by human neutrophils. Biochem Biophys Res Commun. 1993 Jan 29;190(2):660–667. doi: 10.1006/bbrc.1993.1099. [DOI] [PubMed] [Google Scholar]
  4. Choi A. M., Jacoby D. B. Influenza virus A infection induces interleukin-8 gene expression in human airway epithelial cells. FEBS Lett. 1992 Sep 14;309(3):327–329. doi: 10.1016/0014-5793(92)80799-m. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Churchill L., Chilton F. H., Resau J. H., Bascom R., Hubbard W. C., Proud D. Cyclooxygenase metabolism of endogenous arachidonic acid by cultured human tracheal epithelial cells. Am Rev Respir Dis. 1989 Aug;140(2):449–459. doi: 10.1164/ajrccm/140.2.449. [DOI] [PubMed] [Google Scholar]
  7. Collins P. D., Jose P. J., Williams T. J. The sequential generation of neutrophil chemoattractant proteins in acute inflammation in the rabbit in vivo. Relationship between C5a and proteins with the characteristics of IL-8/neutrophil-activating protein 1. J Immunol. 1991 Jan 15;146(2):677–684. [PubMed] [Google Scholar]
  8. Cromwell O., Hamid Q., Corrigan C. J., Barkans J., Meng Q., Collins P. D., Kay A. B. Expression and generation of interleukin-8, IL-6 and granulocyte-macrophage colony-stimulating factor by bronchial epithelial cells and enhancement by IL-1 beta and tumour necrosis factor-alpha. Immunology. 1992 Nov;77(3):330–337. [PMC free article] [PubMed] [Google Scholar]
  9. Davies R. J., Devalia J. L. Asthma. Epithelial cells. Br Med Bull. 1992 Jan;48(1):85–96. doi: 10.1093/oxfordjournals.bmb.a072544. [DOI] [PubMed] [Google Scholar]
  10. Donnelly S. C., Strieter R. M., Kunkel S. L., Walz A., Robertson C. R., Carter D. C., Grant I. S., Pollok A. J., Haslett C. Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet. 1993 Mar 13;341(8846):643–647. doi: 10.1016/0140-6736(93)90416-e. [DOI] [PubMed] [Google Scholar]
  11. Gosset P., Tsicopoulos A., Wallaert B., Vannimenus C., Joseph M., Tonnel A. B., Capron A. Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol. 1991 Oct;88(4):561–571. doi: 10.1016/0091-6749(91)90149-i. [DOI] [PubMed] [Google Scholar]
  12. Larsen C. G., Anderson A. O., Appella E., Oppenheim J. J., Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science. 1989 Mar 17;243(4897):1464–1466. doi: 10.1126/science.2648569. [DOI] [PubMed] [Google Scholar]
  13. Lynch J. P., 3rd, Standiford T. J., Rolfe M. W., Kunkel S. L., Strieter R. M. Neutrophilic alveolitis in idiopathic pulmonary fibrosis. The role of interleukin-8. Am Rev Respir Dis. 1992 Jun;145(6):1433–1439. doi: 10.1164/ajrccm/145.6.1433. [DOI] [PubMed] [Google Scholar]
  14. Marini M., Vittori E., Hollemborg J., Mattoli S. Expression of the potent inflammatory cytokines, granulocyte-macrophage-colony-stimulating factor and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma. J Allergy Clin Immunol. 1992 May;89(5):1001–1009. doi: 10.1016/0091-6749(92)90223-o. [DOI] [PubMed] [Google Scholar]
  15. Martich G. D., Danner R. L., Ceska M., Suffredini A. F. Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents. J Exp Med. 1991 Apr 1;173(4):1021–1024. doi: 10.1084/jem.173.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mattoli S., Miante S., Calabrò F., Mezzetti M., Fasoli A., Allegra L. Bronchial epithelial cells exposed to isocyanates potentiate activation and proliferation of T-cells. Am J Physiol. 1990 Oct;259(4 Pt 1):L320–L327. doi: 10.1152/ajplung.1990.259.4.L320. [DOI] [PubMed] [Google Scholar]
  17. Mukaida N., Gussella G. L., Kasahara T., Ko Y., Zachariae C. O., Kawai T., Matsushima K. Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line. Immunology. 1992 Apr;75(4):674–679. [PMC free article] [PubMed] [Google Scholar]
  18. Mukaida N., Shiroo M., Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989 Aug 15;143(4):1366–1371. [PubMed] [Google Scholar]
  19. Nettesheim P., Ferriola P., Steigerwalt R., Robertson A., Rundhaug J. The role of growth factors in the regulation of proliferation of tracheobronchial epithelium. Chest. 1992 Mar;101(3 Suppl):23S–24S. doi: 10.1378/chest.101.3_supplement.23s. [DOI] [PubMed] [Google Scholar]
  20. Ohkawara Y., Yamauchi K., Tanno Y., Tamura G., Ohtani H., Nagura H., Ohkuda K., Takishima T. Human lung mast cells and pulmonary macrophages produce tumor necrosis factor-alpha in sensitized lung tissue after IgE receptor triggering. Am J Respir Cell Mol Biol. 1992 Oct;7(4):385–392. doi: 10.1165/ajrcmb/7.4.385. [DOI] [PubMed] [Google Scholar]
  21. Rolfe M. W., Kunkel S. L., Standiford T. J., Chensue S. W., Allen R. M., Evanoff H. L., Phan S. H., Strieter R. M. Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking. Am J Respir Cell Mol Biol. 1991 Nov;5(5):493–501. doi: 10.1165/ajrcmb/5.5.493. [DOI] [PubMed] [Google Scholar]
  22. Standiford T. J., Kunkel S. L., Basha M. A., Chensue S. W., Lynch J. P., 3rd, Toews G. B., Westwick J., Strieter R. M. Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. J Clin Invest. 1990 Dec;86(6):1945–1953. doi: 10.1172/JCI114928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Standiford T. J., Kunkel S. L., Rolfe M. W., Evanoff H. L., Allen R. M., Strieter R. M. Regulation of human alveolar macrophage- and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone. Am J Respir Cell Mol Biol. 1992 Jan;6(1):75–81. doi: 10.1165/ajrcmb/6.1.75. [DOI] [PubMed] [Google Scholar]
  24. Tobler A., Meier R., Seitz M., Dewald B., Baggiolini M., Fey M. F. Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and IL-6, but not of M-CSF in human fibroblasts. Blood. 1992 Jan 1;79(1):45–51. [PubMed] [Google Scholar]
  25. Warringa R. A., Koenderman L., Kok P. T., Kreukniet J., Bruijnzeel P. L. Modulation and induction of eosinophil chemotaxis by granulocyte-macrophage colony-stimulating factor and interleukin-3. Blood. 1991 Jun 15;77(12):2694–2700. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES