Flagellin is the principal inducer of the antimicrobial peptide S100A7c (psoriasin) in human epidermal keratinocytes exposed to Escherichia coli.
Epidermal keratinocytes (KCs) express antimicrobial peptides as a part of the innate immune response. It has recently been shown that the culture supernatant of Escherichia coli induces the expression of S100A7c (psoriasin) in KCs and that S100A7c efficiently kills E. coli. Here we have investigated which of the microbial components triggers the up-regulation of S100A7c expression. Exposure of human primary KCs to ligands of the human Toll-like receptors (TLRs) revealed that only the TLR5 ligand flagellin strongly induced the expression of S100A7c mRNA and protein, whereas all other TLR ligands had no significant effect. In contrast to the supernatant from flagellated wild-type (WT) E. coli, the supernatant of a flagellin-deficient E. coli strain (DeltaFliC) did not induce S100A7c expression. Small interfering RNA-mediated knockdown of TLR5 expression suppressed the ability of KCs to up-regulate S100A7c expression in response to both flagellin and WT E. coli supernatant. Taken together, our data demonstrate that bacterial flagellin is essential and sufficient for the induction of S100A7c expression in KCs by E. coli.
Abtin
Arby
A
Department of Dermatology, Medical University of Vienna, Waehringer Guertal 18-20, 1090 Vienna, Austria.
Eckhart
Leopold
L
Mildner
Michael
M
Gruber
Florian
F
Schröder
Jens-Michael
JM
Tschachler
Erwin
E
D002135:Calcium-Binding Proteins / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers; D004817:Epidermis / Q000382:microbiology* / Q000502:physiology*; D004926:Escherichia coli / Q000502:physiology*; D005408:Flagellin / Q000378:metabolism*; D052816:Foreskin / Q000166:cytology / Q000382:microbiology / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000382:microbiology / Q000502:physiology*; D008297:Male; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D005408:Flagellin; C416532:flaB flagellin; D012313:RNA