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The release of pro‐inflammatory cytokines is mediated via mitogen‐activated protein kinases rather than by the inflammasome signalling pathway in keratinocytes
Author(s) -
Ondet Thomas,
MuscatelliGroux Béatrice,
Coulouarn Cédric,
Robert Sacha,
Gicquel Thomas,
Bodin Aude,
Lagente Vincent,
Grimaud JeanAlexis
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12765
Subject(s) - microbiology and biotechnology , tlr2 , chemokine , inflammasome , signal transduction , kinase , biology , p38 mitogen activated protein kinases , innate immune system , mitogen activated protein kinase , toll like receptor , hacat , protein kinase a , chemistry , tlr4 , receptor , biochemistry , in vitro
SUMMARY Toll‐like receptors ( TLR s) are expressed in the skin and airway epithelial tissues, which are the most important sites of host–pathogen interactions. TLR s 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 TLR 4, 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 TLR 2, IL ‐6 and IL ‐8/chemokine (C‐X‐C motif) ligand 8 CXCL 8 in the keratinocyte cell line HaCaT. Furthermore, MSU promoted the phosphorylation of extracellular signal‐regulated kinase 1/2 and MAPK 14/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/ CXCL 8 chemokine (C‐X‐C motif) ligand 8 and TLR 2.