IL-33 regulates cytokine production and neutrophil recruitment via the p38 MAPK-activated kinases MK2/3

Pierre C McCarthy, Iain R Phair, Corinna Greger, Katerina Pardali, Victoria A McGuire, Matthias Gaestel, J Simon C Arthur

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


IL-33 is an IL-1-related cytokine that can act as an alarmin when released from necrotic cells. Once released, it can target various immune cells including mast cells, innate lymphoid cells and T cells to elicit a Th2-like immune response. We show here that bone marrow-derived mast cells produce IL-13, IL-6, TNF, GM-CSF, CCL3 and CCL4 in response to IL-33 stimulation. Inhibition of the p38 MAPK, or inhibition or knockout of its downstream kinases MK2 and MK3, blocked the production of these cytokines in response to IL-33. The mechanism downstream of MK2/3 was cytokine specific; however, MK2 and MK3 were able to regulate TNF and GM-CSF mRNA stability. Previous studies in macrophages have shown that MK2 regulates mRNA stability via phosphorylation of the RNA-binding protein TTP (Zfp36). The regulation of cytokine production in mast cells was, however, independent of TTP. MK2/3 were able to phosphorylate the TTP-related protein Brf1 (Zfp36 l1) in IL-33-stimulated mast cells, suggesting a mechanism by which MK2/3 might control mRNA stability in these cells. In line with its ability to regulate in vitro IL-33-stimulated cytokine production, double knockout of MK2 and 3 in mice prevented neutrophil recruitment following intraperitoneal injection of IL-33.

Original languageEnglish
Pages (from-to)54-71
Number of pages18
JournalImmunology and Cell Biology
Issue number1
Publication statusPublished - Jan 2019
Externally publishedYes

Bibliographical note

©2018 The Authors Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc.


  • IL-13
  • IL-33
  • MK2
  • Myd88
  • mast cell
  • p38 MAPK

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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