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Updated: Aug 15, 2025
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Uncoupling melanogenesis from proliferation in epidermal melanocytes responding to stimulation with psoriasis-related
Yun-Zhu Yao1, Zhi-Kai Liao1, Shan Jiang1
1Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, China.
Background:
Few studies have addressed the impact of the psoriasis-related proinflammatory cytokines on the proliferation and melanogenesis of melanocytes (MCs) in lesional psoriatic skin.
Objective:
We investigated the effects of TNFα, IL17A, and IL8 on the proliferation and melanin synthesis of MCs.
Methods:
Skin specimens were biopsied from patients with psoriasis vulgaris at the active stage, or from the tail skin of Dct-LacZ mice with imiquimod (IMQ)-induced psoriasiform dermatitis. Cultured keratinocytes (KCs), MCs, and human skin explants were used in this study. The numbers of MCs were measured via β-galactosidase staining, EdU incorporation and HMB45 immunohistochemical staining. The expression of human β-defensin 3 (hBD3) in KCs was silenced by siRNA, the conditioned medium (CM) from siRNA-transfected KCs was used to treat MCs, then followed by αMSH stimulation. The melanogenesis-related genes were examined by using qRT-PCR and western blotting.
Results:
The increased number of MCs and decreased melanin content were highly relevant to the enhanced expression of IL8 and BD3 both in human psoriatic skin and in IMQ-treated mouse tail skin. IL8 expression in KCs and CXCR2 expression in MCs was significantly increased by IL17A and TNFα, the αMSH-induced upregulations of microphthalmia-associated transcription factor (MITF) and tyrosinase in MCs were abrogated by the CM from hBD3-unsilenced KCs, but not from hBD3-silenced KCs.
Conclusion:
Our results suggest the roles of IL8-CXCR2 activation in promoting MC proliferation and of BD3 upregulation in reducing melanogenesis. These findings have been implicated in the underlying mechanism that active psoriasis prefers hypopigmentation despite chronic inflammation.
Insights
Psoriasis inflammation increases melanocyte numbers via IL8-CXCR2 but reduces melanin production through BD3. This explains hypopigmentation in active psoriasis despite chronic inflammation.
Area of Science:
- Dermatology
- Immunology
- Cell Biology
Background:
- Psoriasis involves chronic inflammation, but its effects on melanocytes (MCs) and melanin synthesis in lesional skin are not well understood.
- Proinflammatory cytokines like TNFα, IL17A, and IL8 are key mediators in psoriasis pathogenesis.
Purpose of the Study:
- To investigate the impact of TNFα, IL17A, and IL8 on melanocyte proliferation and melanin synthesis.
- To elucidate the roles of IL8 and human beta-defensin 3 (BD3) in psoriatic skin pigmentation.
Main Methods:
- Analysis of lesional psoriatic skin and imiquimod-induced psoriasiform dermatitis mouse models.
- In vitro studies using cultured keratinocytes (KCs), melanocytes (MCs), and human skin explants.
- Assessment of MC proliferation via staining and EdU incorporation; melanogenesis via gene expression and protein analysis.
Main Results:
- Increased MC numbers and reduced melanin content correlated with elevated IL8 and BD3 expression in psoriatic skin.
- IL17A and TNFα upregulated IL8 in KCs and CXCR2 in MCs.
- BD3 in KCs inhibited αMSH-induced melanogenesis-related gene expression in MCs.
Conclusions:
- IL8-CXCR2 signaling promotes MC proliferation in psoriasis.
- Upregulated BD3 contributes to reduced melanogenesis, explaining hypopigmentation in active psoriasis.
- Findings reveal mechanisms linking inflammation, melanocyte behavior, and pigmentation changes in psoriasis.
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