Because little is known about how the innate immune response influences skin pigmentation, we examined whether Toll-like receptor (TLR) agonists participate in melanogenesis and melanosome transportation. We observed that TLR2/2 agonist HKLM and TLR3 agonist Poly(I:C) increased the amount of extracellular melanin from primary human epidermal melanocytes. HKLM, but not Poly(I:C), increased the melanogenic genes such as tyrosinase and dopachrome tautomerase. Poly(I:C) increased the expression of Rab27A, a molecule that facilitates melanosome transport to perimembranous actin filament. UVB irradiation induced Rab27A and melanosome transportation in a similar manner of Poly(I:C). SiRNA for TLR3 or Rab27A suppressed the perimembranous accumulation of Gp100-positive vesicles in melanocytes and decreased melanin transfer to neighboring keratinocytes induced by both Poly(I:C) and UVB. These results suggest that the microenvironment in the epidermis and innate immune stimuli, such as microbiome and ultraviolet represented here by TLR2 and TLR3 agonists, could affect the melanogenesis in human melanocytes.

Cutaneous leiomyomas are benign smooth muscle tumors that are occasionally painful. The mechanism of pain related to leiomyoma is not fully understood. To investigate the possible involvement of algoneic factors in pain from cutaneous leiomyomas. We present a case of cutaneous leiomyoma with severe, diffused pain in a large area and collected 10 more specimens of cutaneous leiomyoma with or without pain in patient histories. We immunohistochemiacally examined the expression of algoneic factors: serotonin, histamin, Substance P, PGE2, BDKRB2, VR1 and CGRP. We compared the pain area and expression of algoneic factors to reveal possible correlations. We describe here a patient with a cutaneous leiomyoma 1-cm in diameter, which caused severe pain diffused throughout an area of 20-cm around the tumor. The pain completely resolved after surgical excision of the leiomyoma. We observed that the leiomyoma cells expressed CGRP, PGE2 and VR1 in this case. We found a positive correlation between VR1 and PGE2 expression in the leiomyoma cells and areas with pain around the tumors among 11 specimens in total. VR1 and PGE2 might be key algogenic substances in painful leiomyoma.