Regulation and function of the IL-1 family cytokine IL-1F9 in human bronchial epithelial cells

Regina T. Chustz, Deepti R. Nagarkar, Julie A. Poposki, Silvio Favoreto, Pedro C. Avila, Robert P. Schleimer, Atsushi Kato*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

The IL-1 family of cytokines, which now includes 11 members, is well known to participate in inflammation. Although the most recently recognized IL-1 family cytokines (IL-1F5-11) have been shown to be expressedinairway epithelial cells, the regulation of their expression and function in the epitheliumhas not been extensively studied.We investigated the regulation of IL-1F5-11 in primary normal human bronchial epithelial cells. Messenger (m)RNAs for IL-1F6 and IL-1F9, but not IL-1F5, IL-1F8 or IL-1F10, were significantly up-regulated by TNF, IL-1β, IL-17 and the Toll-like receptor (TLR)3 ligand doublestranded (ds)RNA.mRNAsfor IL-1F7 and IL-1F11 (IL-33) were weakly up-regulatedbysomeof the cytokines tested. Notably,mRNAsfor IL-1F6 and IL-1F9 were synergistically enhanced by the combination of TNF/IL-17 or dsRNA/IL-17. IL-1F9 protein was detected in the supernatant following stimulation with dsRNA or a combination of dsRNA and IL-17. IL-1F6 protein was detected in the cell lysate but was not detected in the supernatant. We screened for the receptor for IL-1F9 and found that lung fibroblasts expressed this receptor. We found that IL-1F9 activated mitogen-activated protein kinases and the transcription factor NF-κB in primary normal human lung fibroblasts. IL-1F9 also stimulated the expression of the neutrophil chemokines IL-8 and CXCL3 and the Th17 chemokine CCL20 in lung fibroblasts. These results suggest that epithelial activation by TLR3 (e.g., by respiratory viral infection) and exposure to cytokines from Th17 cells (IL-17) and inflammatory cells (TNF) may amplify neutrophilic inflammation in the airway via induction of IL-1F9 and activation of fibroblasts.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number1
DOIs
StatePublished - Jul 1 2011

Keywords

  • Human bronchial epithelial cells
  • Human lung fibroblasts
  • IL-17
  • IL-1F9
  • Toll-like receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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