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Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
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Chronic Histamine Exposure Promotes Melanogenesis via ORAI1-STIM1-Mediated Calcium Signaling Remodeling
Nhung Thi Hong Van1,2,3, Hong Thi Lam Phan4,5,6, Minh Tuan Nguyen7
1Department of Physiology, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
International Journal of Molecular Sciences
|February 27, 2026
Summary
Histamine triggers skin darkening by remodeling calcium channels. Blocking the ORAI1-STIM1 complex in cells reduces this effect, offering a new target for post-inflammatory hyperpigmentation treatments.
Area of Science:
- Dermatology
- Cell Biology
- Biochemistry
Background:
- Post-inflammatory hyperpigmentation (PIH) involves excessive melanin production after skin inflammation.
- Histamine stimulates melanogenesis via H2 receptors, but calcium signaling pathways are unclear.
Purpose of the Study:
- To investigate the ORAI1-STIM1 complex's role in histamine-induced melanogenesis.
- To explore calcium signaling mechanisms in PIH.
Main Methods:
- Utilized B16F10 melanoma cells and normal human epidermal melanocytes (NHEMs).
- Assessed melanin content, calcium (Ca2+) influx, and store-operated Ca2+ entry (SOCE).
- Employed histamine, H2 antagonist famotidine, Ca2+ chelators, ORAI1 inhibitors (BTP-2, Synta-66), and siRNA silencing.
Main Results:
- Histamine increased melanin content, blocked by famotidine.
- Chronic histamine exposure enhanced SOCE capacity (approx. 2.8-fold).
- Inhibition/silencing of ORAI1 or STIM1 significantly suppressed histamine-induced melanogenesis.
Conclusions:
- Chronic histamine exposure induces PIH via ORAI1-STIM1-mediated SOCE remodeling.
- The ORAI1-STIM1 complex is a potential therapeutic target for PIH and inflammatory pigmentary disorders.
Keywords:
H2 receptorORAI1calcium signalinghistaminemelanogenesispost-inflammatory hyperpigmentationprimary human melanocytesstore-operated calcium entryMore Related Videos
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