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Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule

Sally E Dickinson1,2,3, Prajakta Vaishampayan1, Jana Jandova1,4

  • 1The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona, USA.

JID Innovations : Skin Science From Molecules to Population Health
|February 8, 2024
PubMed

Insights

Topical PD-L1 inhibition with BMS-202 protects skin from UV damage. This small molecule reduces inflammation and immune responses, showing promise for preventing photodamage.

Area of Science:

  • Dermatology
  • Immunology
  • Molecular Biology

Background:

  • The immune checkpoint ligand PD-L1 is a target for skin cancer therapy.
  • PD-L1 may offer preventive benefits against solar UV light-induced skin damage.
  • PD-L1 is known to be upregulated in cutaneous squamous cell carcinoma.

Purpose of the Study:

  • To investigate the role of PD-L1 in acute keratinocytic photodamage.
  • To evaluate the effects of small-molecule pharmacological inhibition of PD-L1.
  • To assess the potential of PD-L1 antagonism for skin protection against UV damage.

Main Methods:

  • Immunohistochemical and proteomic analyses of human skin cohorts.
  • Topical application of PD-L1 inhibitor BMS-202 in mouse models and human keratinocytes.
  • RT-qPCR and NanoString nCounter transcriptomic analysis to assess gene expression.
  • Analysis of UV-induced activator protein-1 transcriptional activity and procaspase-3 cleavage.

Main Results:

  • Epidermal PD-L1 was upregulated in response to chronic photodamage.
  • BMS-202 significantly attenuated UV-induced activator protein-1 activity and inflammatory gene expression.
  • BMS-202 inhibited UV-induced procaspase-3 cleavage, a marker of photodamage.
  • Transcriptomic analysis confirmed downregulation of innate immunity and inflammation, with upregulation of immune response pathways.

Conclusions:

  • Topical PD-L1 antagonism with BMS-202 shows promise for protecting skin against photodamage.
  • BMS-202 effectively antagonizes UV-induced PD-L1 expression at both mRNA and protein levels.
  • Targeting PD-L1 offers a potential strategy for preventing UV-induced skin damage and inflammation.
Keywords:
InflammationPD-L1SKH-1 mouseSkin photoprotectionUV light

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