Ann Dermatol.  2010 Nov;22(4):486-489. 10.5021/ad.2010.22.4.486.

Activation of Toll-like Receptors 1, 2, 4, 5, and 7 on Human Melanocytes Modulate Pigmentation

Affiliations
  • 1Department of Dermatology, Center for Cell Death Regulating Biodrugs, Ajou University School of Medicine, Suwon, Korea. hykang@ajou.ac.kr

Abstract

Human melanocytes are not simply pigment-producing cells. It may be part of the inflammatory response, during which the pigmentary system may produce more melanin or suppress melanization. Toll-like receptors (TLRs) have been implicated in both innate host defense against pathogens and inflammatory response. Therefore, it may be possible that activation of TLRs in melanocytes may play a role in the modulation of melanogenesis. In this study, we investigated whether normal human melanocytes expressed TLRs and analyzed pigmentation changes upon TLR stimulation. The expression of TLR1~10 mRNA in cultured human melanocyte was analyzed using RT-PCR, Western blotting and immunocytochemistry. Human melanocytes constitutively express mRNA and protein for TLR2, 3, 4, 5, 7, 9 and 10. Stimulation of TLR1/2 and 4 with Pam3CSK4 and lipopolysaccharide induced pigmentation of melanocytes. Activation of TLR5 and 7 with flagellin and imiquimod treatments reduced pigmentation of melanocytes and zebrafish. In summary, the results provided evidence for TLRs expression in normal human melanocytes. It is speculated that a response of melanocyte to TLR ligands may play a role in the pigmentary change in the skin.

Keyword

Melanocytes; Pigmentation; Toll-like receptors

MeSH Terms

Aminoquinolines
Blotting, Western
Flagellin
Humans
Immunohistochemistry
Ligands
Melanins
Melanocytes
Pigmentation
RNA, Messenger
Skin
Toll-Like Receptors
Zebrafish
Aminoquinolines
Flagellin
Ligands
Melanins
RNA, Messenger
Toll-Like Receptors

Figure

  • Fig. 1 Toll-like receptors (TLRs) are expressed in human melanocytes. (A) Expression of TLR1-10 was assessed by RT-PCR. The protein expression was detected by immunocytochemistry (B: ×200) and Western blotting (C). Negative controls were made by applying normal rabbit serum before treatment with primary antibody.

  • Fig. 2 Effects of toll-like receptor (TLR) ligands on pigmentation. Melanocytes were treated with Pam3CSK4, PolyI:C, LPS, flagellin or imiquimod, a ligand (1~10µg/ml) of TLR1/2, 3, 4, 5, or 7 for 5 days. (A) Melanin content was determined by measuring the absorbance at 490 nm. The values indicate the mean of three independent experiments±SD. *p<0.05. (B) Zebrafish was treated with ligands (20 or 40 µg/ml) for 24 hrs and was visualized under microscope. The results were reproducible in three independent experiments. Magnified view (Inset).


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