Human melanocytes express functional Toll-like receptor 4.

Abstract

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.

OBJECTIVES: 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.