Molecular regulation of interleukin-13 and monocyte chemoattractant protein-1 expression in human mast cells by interleukin-1β

Steven A. Lee, S. Matthew Fitzgerald, Shau K. Huang, Chuanfu Li, David S. Chi, Denise M. Milhorn, Guha Krishnaswamy

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Mast cells play pivotal roles in immunoglobulin (Ig) E-mediated airway inflammation, expressing interleukin (IL)-13 and monocyte chemoattractant protein-1 (MCP-1), which in turn regulate IgE synthesis and/or inflammatory cell recruitment. The molecular effects of IL-1β on cytokine expression by human mast cells (HMC) have not been studied well. In this report, we provide evidence that human umbilical cord blood-derived mast cells (CBDMC) and HMC-1 cells express the type 1 receptor for IL-1. We also demonstrate that IL-1β and tumor necrosis factor-α are able to induce, individually or additively, dose-dependent expression of IL-13 and MCP-1 in these cells. The induction of IL-13 and MCP-1 gene expression by IL-1β was accompanied by the activation of IL-1 receptor-associated kinase and translocation of the transcription factor, nuclear factor (NF) κB into the nucleus. Accordingly, Bay-11 7082, an inhibitor of NF-κB activation, inhibited IL-1β-induced IL-13 and MCP-1 expression. IL-1β also induced IL-13 promoter activity while enhancing the stability of IL-13 messenger RNA transcripts. Dexamethasone, a glucocorticoid, inhibited IL-1β-induced nuclear translocation of NF-κB and also the secretion of IL-13 from mast cells. Our data suggest that IL-1β can serve as a pivotal costimulus of inflammatory cytokine synthesis in human mast cells, and this may be partly mediated by IL-1 receptor-binding and subsequent signaling via nuclear translocation of NF-κB. Because IL-1β is a ubiquitously expressed cytokine, these findings have important implications for non-IgE-mediated signaling in airway mast cells as well as for innate immunity and airway inflammatory responses, such as observed in extrinsic and intrinsic asthma.

Original languageEnglish
Pages (from-to)283-291
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume31
Issue number3
DOIs
Publication statusPublished - Sep 1 2004

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

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