Abstract
Epidermal keratinocytes secrete cytokines, chemokines, and anti-microbial peptides
in response to various microbial pathogens and their components including lipopolysaccharide
(LPS). To identify the receptor(s) involved in the anti-microbial responses of epidermal
keratinocytes, we analyzed expression of CD14, Toll-like receptor 2 (TLR2), and TLR4
on cultured normal human epidermal keratinocytes (NHEK). Although CD14 and TLR2 mRNA
were expressed in cultured NHEK, only TLR2 was detected on the cell surface. Cultured
NHEK did not express TLR4 mRNA or protein. Commercial LPS preparations could stimulate
epidermal keratinocytes to produce β-defensin-2 and IL-8, and the LPS response was
inhibited with mAb specific for TLR2, but not for CD14 or TLR4. Repurified LPS and
lipid A did not stimulate epidermal keratinocytes, whereas peptidoglycan (PGN) from
Gram-positive bacteria and yeast cell wall particle induced β-defensin-2 and IL-8
production. Thus, cultured NHEK express functional TLR2, but not CD14 or TLR4, and
the “LPS” response of epidermal keratinocytes shown in the previous studies might
be mediated by TLR2-dependent recognition of non-LPS bacterial components contaminating
in commercial LPS preparations. In the normal human skin, however, epidermal keratinocytes
expressed both TLR2 and TLR4. Because TLR4 was induced in epidermal keratinocytes
by in vitro stimulation with PGN from Gram-positive bacteria, constitutive expression
of TLR4 on epidermal keratinocytes in vivo might also be induced by continuous recognition
of the resident skin flora containing Gram-positive bacteria through TLR2.
Keywords
Abbreviations:
NHEK, normal human epidermal keratinocytes (), HBD2, human β-defensin-2 (), TLR, Toll-like receptor (), PRR, pattern recognition receptor (), PAMP, pathogen-associated molecular pattern (), PGN, peptidoglycan ()To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
July 25,
2002
Received in revised form:
July 24,
2002
Received:
June 13,
2002
Identification
Copyright
© 2002 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
