Ultraviolet a induces endoplasmic reticulum stress response in human dermal fibroblasts.

The endoplasmic reticulum (ER) stress response is a cytoprotective mechanism against the accumulation of unfolded proteins in the ER (ER stress) that consists of three response pathways (the ATF6, IRE1 and PERK pathways) in mammals. These pathways regulate the transcription of ER-related genes through specific cis-acting elements, ERSE, UPRE and AARE, respectively. Because the mammalian ER stress response is markedly activated in professional secretory cells, its main function was thought to be to upregulate the capacity of protein folding in the ER in accordance with the increased synthesis of secretory proteins.

The epidermal stem cell factor is over-expressed in lentigo senilis: implication for the mechanism of hyperpigmentation.

We previously reported that accentuated expression of the endothelin-1 (ET-1)/endothelin B receptor (ET(B)R) cascade is involved in the mechanism of hyperpigmentation in lentigo senilis (LS) lesions. The paracrine mechanism underlying ultraviolet B (UVB)-induced hyperpigmentation in the skin may involve the stimulation of the ET-1/ET(B)R cascade as well as the stem cell factor (SCF)/SCF receptor cascade. Therefore, we used RT-PCR and immunohistochemistry to determine whether accentuated expression of the SCF/SCF receptor cascade is also associated with the mechanism of hyperpigmentation in epidermal LS lesions.

Sphingosylphosphorylcholine is a Melanogenic Stimulator for Human Melanocytes.

As lysosphingolipids have multiple bio-modulator functions in various types of cells, we measured the biological effects of sphingosylphosphorylcholine (SPC) on cultured human melanocytes to determine whether these lysosphingolipids have the potential to activate these cells. The addition of SPC to cultured human melanocytes significantly stimulated DNA synthesis assessed by [3H]thymidine and melanogenesis assessed by the release of [3H]H2O (tyrosinase activity), the incorporation of [14C]thiouracil (melanin synthesis) and dopa-oxidase activity. Reverse transcription-polymerase chain reaction of RNA isolated from human melanocytes exposed to SPC revealed an upregulation of mRNA transcripts for tyrosinase, microphthalmia-associated transcription factor-M, endothelin B receptor and the stem cell factor receptor, c-kit.

Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus.

The stratum corneum of the skin of patients with atopic dermatitis is highly susceptible to colonization by various bacteria, including Staphylococcus aureus. The defense system of the skin against bacterial invasion appears to be significantly disrupted in atopic dermatitis skin, but little is known about the defense mechanism(s) involved. As one sphingolipid metabolite, sphingosine is known to exert a potent antimicrobial effect on S.