Oral communication, S2 Presidential Lecture

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Pigment Production for Maintaining Epidermal Homeostasis: Lessons from Keratinocytes and Melanocytes

The skin is a unique organ that is covered with the stratum corneum and is continuously exposed to external stressful environments, such as atmospheric oxygen and solar radiations. These environmental factors may influence the homeostasis of keratinocytes and melanocytes by changing the production of oxidative stress-protective substances, such as bilirubin and melanin. Heme oxygenase-1 (HO-1) is an essential enzyme in heme catabolism and cleaves heme to form biliverdin, iron, and carbon monoxide. Biliverdin is immediately reduced to bilirubin, a physiological radical scavenger. HO-1 is expressed in all types of skin cells, including keratinocytes and melanocytes. In fact, bilirubin is accumulated in the stratum corneum in normal human skin, indicating the degradation of heme in keratinocytes. Keratinocytes migrate toward the surface of the skin and gradually lose their nuclei to form the stratum corneum. It is therefore conceivable that keratinocytes may contribute to the preservation of iron. On the other hand, lipocalin-type prostaglandin D synthase (L-PGDS) is the enzyme that catalyzes the synthesis of prostaglandin D2 (PGD2) and is expressed in melanocytes, but not in keratinocytes. PGD2 and its metabolites are known to induce HO-1 expression. Importantly, L-PGDS is actively secreted to the extracelluar space and also functions as a transporter for lipophilic ligands, including bilirubin and all-trans retinoic acid (RA). We have provided evidence that L-PGDS expression may regulate the proliferation activity of the melanocyte-lineage cells through RA. The human skin therefore contains the regulatory network for production of melanin and bilirubin, thereby maintaining epidermal homeostasis.

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