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Expression, subcellular localization and cytokinic modulation of Toll-like receptors (TLRs) in normal human keratinocytes: TLR2 up-regulation in psoriatic skin


European Journal of Dermatology. Volume 17, Number 6, 497-506, November-December 2007, Investigative report

Free Article  

Author(s) : Édouard Begon, Laurence Michel, Béatrice Flageul, Isabelle Beaudoin, Francette Jean-Louis, Hervé Bachelez, Louis Dubertret, Philippe Musette

Summary : The aim of the research described here was to investigate the expression of Toll-like receptors (TLRs) in normal human keratinocytes, to study its modulation by proinflammatory cytokines, and to characterize the function of the latter within the epidermis. Our results demonstrate that normal human keratinocytes may present an intra-cytoplasmic expression of TLR2, TLR3, and TLR4. Exposure of keratinocytes to IFN-γ and TNF-α increased intra-cytoplasmic expression and led to partial translocation at the cell surface. Keratinocyte activation by TLR2, TLR3, and TLR4 ligands led to the nuclear translocation of NF-κb and the release of proinflammatory cytokines TNF-α and IL-8. In immunochemistry analysis, psoriatic skin showed a strong over-expression of TLR2 in the epidermis compared with normal skin. Our results thus demonstrate large TLR expression in keratinocytes and the functionality of TLRs 2, 3, and 4. TLR2 over-expression in psoriatic skin provides new insights into TLR implication in the pathogenesis of psoriasis, through inappropriate stimulation by infectious or endogen ligands.

Keywords : Toll-like receptor, psoriasis, keratinocytes, tumor necrosis alpha, subcellular localization

 

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