The release of pro-inflammatory cytokines is mediated via mitogen-activated protein kinases rather than by the inflammasome signalling pathway in keratinocytes

Thomas Ondet, Béatrice Muscatelli-Groux, Cédric Coulouarn, Sacha Robert, Thomas Gicquel, Aude Bodin, Vincent Lagente, Jean Alexis Grimaud

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Toll-like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host–pathogen interactions. TLRs recognize the 3-D structures of pathogen-associated molecules and are therefore useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides and monosodium urate (MSU) crystals in the activation of the TLR and NOD-like receptor (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NOD-like receptor P3 and TLR4, both of which are components of inflammasome complexes involved in the activation of interleukin (IL)-1β, were not expressed in keratinocytes. Transcriptomic analysis showed that the combination of MSU and lipopolysaccharide priming did not elicit significant results compared to MSU treatment, which induced the expression of TLR2, IL-6 and IL-8/chemokine (C-X-C motif) ligand 8 CXCL8 in the keratinocyte cell line HaCaT. Furthermore, MSU promoted the phosphorylation of extracellular signal-regulated kinase 1/2 and MAPK14/p38α mitogen-activated protein kinases. We concluded that MSU stimulates a pro-inflammatory response in keratinocytes via mitogen-activated protein kinase pathway to induce production of IL-8/CXCL8 chemokine (C-X-C motif) ligand 8 and TLR2.

Original languageEnglish (US)
Pages (from-to)827-838
Number of pages12
JournalClinical and Experimental Pharmacology and Physiology
Volume44
Issue number7
DOIs
StatePublished - Jul 2017

Keywords

  • MAP kinase
  • inflammation
  • keratinocytes
  • toll-like receptors

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