The TRPM5 Antagonist Triphenylphosphine Oxide Increases Sebaceous Lipogenesis and Modulates Immune Phenotype of Human Sebocytes in a TRPM5-Independent Manner

May 2025 in “ Experimental Dermatology ”

Dorottya Ádám, József Arany, Kinga Tóth, on behalf of the Coll Cancer Richard Peto, T. Nyitrai, Balázs István Tóth, Szilárd Póliska, Christos C. Zouboulis, Attila Oláh

TRPM5 triphenylphosphine oxide sebaceous lipogenesis human sebocytes Akt pathway EGFR pathway diacylglycerol O-acyltransferase-2 interleukin-6 IL-6 IL-8 pro-inflammatory cytokines TPPO DGAT-2

TLDR Triphenylphosphine oxide can increase oil production and reduce inflammation in skin cells without affecting TRPM5.

The study investigates the effects of TRPM5 modulators on human sebocytes, revealing that TRPM5 is not functionally active in these cells. The antagonist triphenylphosphine oxide (TPPO) was found to promote sebaceous lipogenesis and modulate immune responses in a TRPM5-independent manner. TPPO's effects are mediated through Akt and EGFR pathways, leading to increased diacylglycerol O-acyltransferase (DGAT)-2 activity and up-regulation of interleukin (IL)-6, while decreasing IL-8 and other pro-inflammatory cytokines. These findings suggest that TPPO analogues could offer moderate lipogenic and anti-inflammatory benefits for dry skin conditions without direct side effects on sebaceous glands.

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