Interleukin-17 induces hyperresponsive interleukin-8 and interieukin-6 production to tumor necrosis factor-alpha in structural lung cells

A van den Berg*, M Kuiper, M Snoek, W Timens, DS Postma, HM Jansen, R Lutter

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

57 Citations (Scopus)

Abstract

Lung epithelial cells contribute to local inflammation by the production of pro-inflammatory mediators like interleukin (IL)-8 and IL-6. Although their production depends on gene transcription, previous studies showed that post-transcriptional mechanisms modulate IL-8 and IL-6 production. Human lung epithelial cells turn from normoresponsive into hyperresponsive IL-8- and IL-6-producing cells when their IL-8 and IL-6 mRNA degradation is reduced. We hypothesized that IL-17, a mediator predominantly released by memory T cells and present in airways of individuals with asthma, would modulate rather than induce IL-8 and IL-6 production by both human lung epithelial cells and fibroblasts. We show here for both cell types that IL-17 was a weak stimulus of IL-8 and IL-6 production, but markedly enhanced IL-8 and IL-6 responses to another stimulus, such as tumor necrosis factor-alpha. This modulatory effect of IL-17 was paralleled by a reduced IL-8 and IL-6 mRNA degradation, with no effect on IL-8 and IL-6 gene transcription. In conclusion, IL-17 particularly affects post-transcriptional regulation of IL-8 and IL-6 expression leading to enhanced IL-8 and IL-6 responses to secondary stimuli, and is only a weak proinflammatory stimulus by itself. This poses the interesting concept that by releasing IL-17 from memory T cells, the adaptive immune system instructs lung structural cells as part of the innate immune system to respond more vigorously.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume33
Issue number1
DOIs
Publication statusPublished - Jul-2005

Keywords

  • chemokines
  • cytokines
  • inflammation
  • lung
  • NF-KAPPA-B
  • MESSENGER-RNA STABILITY
  • EPITHELIAL H292 CELLS
  • 3'-UNTRANSLATED REGION
  • GENE-EXPRESSION
  • ALLERGIC-ASTHMA
  • IFN-GAMMA
  • TNF-ALPHA
  • IL-17
  • PROTEIN

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