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• W2040687527 abstract "To the Editor: I read with interest the article bySong et al., 2002Song P.I. Park Y.-M. Abraham T. Human keratinocytes express functional CD14 and toll-like receptor 4.J Invest Dermatol. 2002; 119: 424-432Crossref PubMed Scopus (159) Google Scholar. The authors showed that cultured human epidermal keratinocytes constitutively express CD14 and Toll-like receptor 4 (TLR4), and respond to lipopolysaccharide (LPS) in a CD14- and TLR4-dependent manner (Song et al., 2002Song P.I. Park Y.-M. Abraham T. Human keratinocytes express functional CD14 and toll-like receptor 4.J Invest Dermatol. 2002; 119: 424-432Crossref PubMed Scopus (159) Google Scholar). Recently, we reported that cultured human epidermal keratinocytes express functional TLR2 (Kawai et al., 2002Kawai K. Shimura H. Minagawa M. Ito A. Tomiyama K. Ito M. Expression of functional Toll-like receptor 2 on human epidermal keratinocytes.J Dermatol Sci. 2002; 30: 185-194Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar). In contrast to the findings ofSong et al., 2002Song P.I. Park Y.-M. Abraham T. Human keratinocytes express functional CD14 and toll-like receptor 4.J Invest Dermatol. 2002; 119: 424-432Crossref PubMed Scopus (159) Google Scholar, we could not detect CD14 or TLR4 expression on cultured human epidermal keratinocytes (Kawai et al., 2002Kawai K. Shimura H. Minagawa M. Ito A. Tomiyama K. Ito M. Expression of functional Toll-like receptor 2 on human epidermal keratinocytes.J Dermatol Sci. 2002; 30: 185-194Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar). We found that the LPS response of keratinocytes depends on TLR2, rather than CD14 or TLR4 (Kawai et al., 2002Kawai K. Shimura H. Minagawa M. Ito A. Tomiyama K. Ito M. Expression of functional Toll-like receptor 2 on human epidermal keratinocytes.J Dermatol Sci. 2002; 30: 185-194Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar). Because keratinocytes do not respond to repurified LPS or lipid A (Kawai et al., 2002Kawai K. Shimura H. Minagawa M. Ito A. Tomiyama K. Ito M. Expression of functional Toll-like receptor 2 on human epidermal keratinocytes.J Dermatol Sci. 2002; 30: 185-194Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar), the LPS response of keratinocytes may be mediated by TLR2-activating non-LPS bacterial components contaminating in commercial LPS preparations. The discrepancy might be related to the different culture conditions of human epidermal keratinocytes. We have shown that cultured human epidermal keratinocytes can be induced to express TLR4 in response to TLR2-activating bacterial components (Kawai et al., 2002Kawai K. Shimura H. Minagawa M. Ito A. Tomiyama K. Ito M. Expression of functional Toll-like receptor 2 on human epidermal keratinocytes.J Dermatol Sci. 2002; 30: 185-194Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar). Addition of serum to the growth medium may also regulate TLR4 expression on keratinocytes in vitro (Kawai et al., 2002Kawai K. Shimura H. Minagawa M. Ito A. Tomiyama K. Ito M. Expression of functional Toll-like receptor 2 on human epidermal keratinocytes.J Dermatol Sci. 2002; 30: 185-194Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar). Furthermore, we have demonstrated that normal human epidermal keratinocytes express both TLR2 and TLR4 in vivo (Kawai et al., 2002Kawai K. Shimura H. Minagawa M. Ito A. Tomiyama K. Ito M. Expression of functional Toll-like receptor 2 on human epidermal keratinocytes.J Dermatol Sci. 2002; 30: 185-194Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar). These observations indicate that cultured human epidermal keratinocytes do not express TLR4 constitutively, but culture conditions can modulate TLR4 expression on keratinocytes in vitro. Although normal human epidermal keratinocytes cultured in the serum-free growth medium were examined in both studies, serum might be used for the isolation and subculture of keratinocytes and could induce TLR4 expression in the study bySong et al., 2002Song P.I. Park Y.-M. Abraham T. Human keratinocytes express functional CD14 and toll-like receptor 4.J Invest Dermatol. 2002; 119: 424-432Crossref PubMed Scopus (159) Google Scholar. Alternatively, in the study by Song et al keratinocytes might be activated through TLR2 with contaminating bacteria/fungi or necrotic cells, which stimulate cells through TLR2 (Li et al., 2001Li M. Carpio D.F. Zheng Y. An essential role of the NF-κB/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells.J Immunol. 2001; 166: 7128-7135Crossref PubMed Scopus (376) Google Scholar). Our data are consistent with a previous study showing that CD14 is not expressed on cultured human epidermal keratinocytes (Hunyadi et al., 1992Hunyadi J. Simon Jr., M. Kenderessy A.S. Ol´h J. Dobozy A. Expression of adhesion molecules and monocyte markers on cultured human keratinocytes.Eur J Dermatol. 1992; 2: 50-55Google Scholar); however, keratinocytes can be induced to express CD14 in vitro in response to interferon-γ (Hunyadi et al., 1993Hunyadi J. Simon Jr., M. Kenderessy A.S. Dobozy A. Expression of monocyte/macrophage markers (CD13, CD14, CD68) on human keratinocytes in healthy and diseased skin.J Dermatol. 1993; 20: 341-345Crossref PubMed Scopus (22) Google Scholar). Similarly, CD14 is not expressed on human epidermal keratinocytes in normal skin (Hunyadi et al., 1992Hunyadi J. Simon Jr., M. Kenderessy A.S. Ol´h J. Dobozy A. Expression of adhesion molecules and monocyte markers on cultured human keratinocytes.Eur J Dermatol. 1992; 2: 50-55Google Scholar;Kawai et al., 2002Kawai K. Shimura H. Minagawa M. Ito A. Tomiyama K. Ito M. Expression of functional Toll-like receptor 2 on human epidermal keratinocytes.J Dermatol Sci. 2002; 30: 185-194Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar), but is expressed on epidermal keratinocytes in several inflammatory skin diseases (Hunyadi et al., 1993Hunyadi J. Simon Jr., M. Kenderessy A.S. Dobozy A. Expression of monocyte/macrophage markers (CD13, CD14, CD68) on human keratinocytes in healthy and diseased skin.J Dermatol. 1993; 20: 341-345Crossref PubMed Scopus (22) Google Scholar). In conclusion, the contradictory data for CD14 and TLR4 expression on cultured human epidermal keratinocytes obtained in these studies might be due to the different culture conditions. These studies, however, clearly demonstrate that human epidermal keratinocytes are able to express functional CD14 and TLRs, and together support the important role for keratinocytes in innate immune responses in the skin." @default.
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• W2040687527 title "Expression of Functional Toll-Like Receptors on Cultured Human Epidermal Keratinocytes" @default.
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