International Immunology, Vol. 15, No. 6, pp. 721-730,
June 2003
© 2003 Japanese Society for Immunology
Expression and function of Toll-like receptors 2 and 4 in human keratinocytes
1,21 Department of Dermatology and Allergology, University of Szeged, 6701 Szeged, Hungary 2 Dermatological Research Group of the Hungarian Academy of Sciences, 6701 Szeged, Hungary 3 Department of Immunology, Eötvös Loránd University, 2131 Göd, Hungary 4 Department of Forensic Medicine, University of Szeged, 6701 Szeged, Hungary 5 Department of Isotope and Membrane Diagnostics, National Institute of Hematology and Immunology, 1113 Budapest, Hungary 6 Institute of Immunology, Faculty of Medicine, University of Debrecen, 4040 Debrecen, Hungary
Correspondence to: A. Pivarcsi, Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, 6701 Szeged, Hungary. E-mail: andor{at}derma.szote.u-szeged.hu
Transmitting editor: A. Falus
Keratinocytes have the ability to kill pathogenic fungi and bacteria by producing antimicrobial substances. Recent studies suggest that microbial components use signaling molecules of the human Toll-like receptor (TLR) family to transduce signals in various cells. Here we provide evidence that keratinocytes express both TLR2 and TLR4 at the mRNA and protein levels, and show that TLR2 and TLR4 are present in the normal human epidermis in vivo and that their expression is regulated by microbial components. The expression of myeloid differentiation protein gene (MyD88), which is involved in the signaling pathway of many TLR, was also demonstrated in keratinocytes. LPS + IFN-
increased the expression of TLR2 and TLR4 50- and 5-fold respectively. Treatment of keratinocytes with Candida albicans, mannan, Mycobacterium tuberculosis or LPS with IFN- resulted in the activation and nuclear translocation of NF-
B. Inhibition of NF-B blocked the Candida-killing activity of keratinocytes, suggesting that the antimicrobial effect of keratinocytes requires NF-B activation. LPS + IFN-, C. albicans (4 Candida/KC), peptidoglycan (1 µg/ml) or M. tuberculosis extract significantly increased IL-8 gene expression after 3 h of treatment (P < 0.05). The increases over the 0-h level were 15-, 8-, 10.8- and 7-fold, respectively. The microbial compound-induced increase in IL-8 gene expression could be inhibited by anti-TLR2 and anti-TLR4 neutralizing antibodies, suggesting that TLRs are involved in the pathogen-induced expression of this pro-inflammatory cytokine. Our findings stress the importance of the role of keratinocytes as a component of innate immunity.
Keywords: epidermis, host defense, IL-8, innate immunity, NF-B
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