Filaggrin knockdown and Toll-like receptor 3 (TLR3) stimulation enhanced the production of thymic stromal lymphopoietin (TSLP) from epidermal layers.
Keratinocytes constitute the first-line barrier against exogenous antigens and contain Toll-like receptors (TLRs), which function as pattern-recognition molecules to activate antimicrobial innate immune responses. In an effort to ascertain whether or not filaggrin (filament-aggregating protein) expression affected the TLR-mediated responses of keratinocytes, we transfected filaggrin siRNA into HaCaT human keratinocyte cells and determined that thymic stromal lymphopoietin (TSLP) and IL-6 secretion were increased by poly(I:C) stimulus. Additionally, TSLP expression is increased in filaggrin knockdown as well as TLR3 stimulation in reconstituted human epidermal layers. Therefore, the findings of this study show that reduced filaggrin levels may influence innate immune responses via TLR stimuli and may contribute to the pathogenesis of inflammatory skin disease via TSLP expression.
Kyung Ho
KH
Lee
Kyung-Ah
KA
Cho
Ji-Yoon
JY
Kim
Jin-Young
JY
Kim
Ji-Hae
JH
Baek
So-Youn
SY
Woo
Jin-Woo
JW
Kim
D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D000091344:Filaggrin Proteins; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D015850:Interleukin-6; D007381:Intermediate Filament Proteins; D034741:RNA, Small Interfering; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C; D000094632:Thymic Stromal Lymphopoietin