Production of granulocyte-macrophage colony-stimulating factor by cultured human tracheal epithelial cells

L. Churchill, B. Friedman, R. P. Schleimer, D. Proud*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

We have evaluated the capacity of cultured human respiratory epithelial cells (HTE) to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) and have examined the ability of proinflammatory stimuli and of glucocorticoids to modulate the production of GM-CSF by these cells. Conditioned medium (CM) was obtained after 24-hr culture of HTE in the presence or absence of serum (5%) and was assayed for GM-CSF activity using the M-07e cell line, which proliferates in response to GM-CSF and interleukin-3 (IL-3). HTE produced 1.1 ± 0.7 and 2.1 ± 1.5 ng GM-CSF/106 cells in the presence or absence of serum, respectively (n = 4). The identity of this activity as GM-CSF was established by neutralization with specific antibody to GM-CSF, while antibody to IL-3 was without effect. Dexamethasone (10-6 M) inhibited basal GM-CSF release to below the limit of detection of the assay (0.12 ng GM-CSF/ml conditioned media). GM-CSF release was significantly enhanced by 10-6 M histamine (1.6 ± 0.7 versus 2.13 ± 0.8 ng GM-CSF/106 cells; n = 9) and 5 ng/ml interleukin-1 (IL-1) (0.6 ± 0.2 versus 3.2 ± 0.5 ng GM-CSF/106 cells; n = 3). Stimulation of GM-CSF release by IL-1 was dose-/dependent. A significant increase in GM-CSF activity was observed with 0.1 ng/ml, while maximal stimulation occurred at 5 ng/ml IL-1. In kinetic studies, GM-CSF activity was first detected in CM from cells incubated in the absence of stimulus at 8 hr of incubation, and continued to increase up to 24 hr. IL-1-stimulated GM-CSF activity was detected in CM as early as 4 hr and continued to increase significantly up to 24 hr. Thus, human tracheal epithelial cells release GM-CSF and this release is regulated by inflammatory mediators and glucocorticoids.

Original languageEnglish (US)
Pages (from-to)189-195
Number of pages7
JournalImmunology
Volume75
Issue number1
StatePublished - 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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