Human melanocytes express functional Toll-like receptor 4.
BACKGROUND
Melanocytes are not simply pigment-producing cells, but produce substances with a range of biological functions including antimicrobial defense. Recent studies suggest that Toll-like receptors (TLRs) play an important role in the cellular response through the recognition of pathogens.


OBJECTIVE
To investigate whether TLR4 and their adapter molecules are expressed in human melanocytes. The regulation and functional role of TLR4 on cell activation were also investigated.


METHODS
The expression of TLR4 in human melanocytes was determined by using reverse transcription polymerase chain reaction, western blotting, immunochemistry and flow cytometry. In vivo expression of TLR4 in melanocytes of normal human epidermis was detected by immunohistochemical double staining. The effects of gram-negative bacterial derived lipopolysaccharide (LPS) on pigmentation were investigated with the measurement of melanin content.


RESULTS
TLR4 and its adaptor molecule CD14 and myeloid differentiation protein gene (MyD88) were constitutively expressed in cultured human melanocytes. Co-staining of histological human skin sections with TLR4 and a melanocyte marker, gp100, confirmed the expression of TLR4 in melanocytes under physiological conditions. LPS upregulated the expression of TLR4 and MyD88 and induced NF-kappaB nuclear translocation B nuclear translocation in melanocytes. Treatment of LPS increased pigmentation of human melanocytes.


CONCLUSIONS
We demonstrated that functional TLR4 was expressed in human melanocytes. Our findings suggest that TLR4 may play a role in microbial-induced melanogenesis.
Ahn
Joo Hee
JH
Department of Dermatology, Ajou University School of Medicine, Suwon, Korea.
Park
Tae Jun
TJ
Jin
Sun Hee
SH
Kang
Hee Young
HY
D002478:Cells, Cultured; D006801:Humans; D007159:Immunologic Tests; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008543:Melanins / Q000032:analysis; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis; D018613:Microscopy, Confocal; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D058951:gp100 Melanoma Antigen
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D008543:Melanins; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C548637:PMEL protein, human; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D058951:gp100 Melanoma Antigen