S100A15, an antimicrobial protein of the skin: regulation by E. coli through Toll-like receptor 4.
E. coli is a gram-negative bacterium rarely found on human skin. We investigated whether direct interaction of E. coli with keratinocytes might induce an innate immune response through recognition by pattern recognition receptors. The capacity of E. coli to activate innate immune responses and IL-8 induction was investigated. We found that E. coli significantly induced human S100A7 and S100A15 transcript abundance and IL-8 release in cultured primary human keratinocytes. S100A15 is a member of the S100 protein family with previously unknown function. E. coli induced effects could be inhibited by neutralizing Toll-like receptor 4 (TLR4) antibodies, suggesting that E. coli-induced IL-8 and S100A15 expression in human keratinocytes are TLR4 dependent. TLR4-/- mice lacked elevated mS100A15 expression after infection with E. coli in contrast to wild-type mice. In vitro, human S100A15 displayed antimicrobial activity against E. coli. Our findings suggest that E. coli modulates S100A15 and IL-8 expression of keratinocytes by recognition through TLR4.
Büchau
Amanda S
AS
Department of Dermatology, Heinrich-Heine-University, Duesseldorf, Germany. asbuchau@ucsd.edu
Hassan
Mohamed
M
Kukova
Gabriela
G
Lewerenz
Virginia
V
Kellermann
Sabine
S
Würthner
Jens U
JU
Wolf
Ronald
R
Walz
Markus
M
Gallo
Richard L
RL
Ruzicka
Thomas
T
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004926:Escherichia coli / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D002135:Calcium-Binding Proteins; D016209:Interleukin-8; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C510475:S100A7A protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4