Effects of continuous-wave (670-nm) red light on wound healing.

BACKGROUND: Recent work suggests that injuries can heal faster if treated by lasers emitting 670-nm red light. LED lights emitting 670-nm light are now available. This suggests that inexpensive and easy-to-use 670-nm LED lights might help accelerate cutaneous wound healing. OBJECTIVE: The objective was to evaluate the effect of 670-nm LED light on wound healing in SKH-1 hairless mice. METHODS: To study 670-nm light effects on incisional injury, animals were left unexposed or exposed to equal doses of high-, medium-, or low-flux light. Burn injuries were treated with high-flux light or left unexposed. Healing was assessed by measurement of the burn area and the gap remaining to closure of incisional injury. RESULTS: Mice exposed to 670-nm red light showed significantly faster healing than control mice. High, medium, and low fluxes of light were all effective after incisional injury. In burn injury, there was improvement in wound healing initially, but the time to repair was unchanged. CONCLUSIONS: A 670-nm LED red light source accelerates healing in skin of SKH-1 hairless mice after incisional injuries, but is not as effective for burn injuries. These data that suggest red light exposure may be helpful in postoperative wound repair.

Sequential down-regulation of E-cadherin with squamous cell carcinoma progression: loss of E-cadherin via a prostaglandin E2-EP2 dependent posttranslational mechanism.

The incidence of skin cancer is on the rise, with over 1 million new cases yearly. Although it is known that squamous cell cancers (SCC) are caused by UV light, the mechanism(s) involved remains poorly understood. In vitro studies with epithelial cells or reports examining malignant skin lesions suggest that loss of E-cadherin-mediated cell-cell contacts may contribute to SCCs. Other studies show a pivotal role for cyclooxygenase-dependent prostaglandin E2 (PGE2) synthesis in this process. Using chronically UV-irradiated SKH-1 mice, we show a sequential loss of E-cadherin-mediated cell-cell contacts as lesions progress from dysplasia to SCCs. This E-cadherin down-regulation was also evident after acute UV exposure in vivo. In both chronic and acute UV injury, E-cadherin levels declined at a time when epidermal PGE2 synthesis was enhanced. Inhibition of PGE2 synthesis by indomethacin in vitro, targeted deletion of EP2 in primary mouse keratinocyte (PMK) cultures or deletion of the EP2 receptor in vivo abrogated this UV-induced E-cadherin down-regulation. In contrast, addition of PGE2 or the EP2 receptor agonist butaprost to PMK produced a dose- and time-dependent decrease in E-cadherin. We also show that UV irradiation, via the PGE2-EP2 signaling pathway, may initiate tumorigenesis in keratinocytes by down-regulating E-cadherin-mediated cell-cell contacts through its mobilization away from the cell membrane, internalization into the cytoplasm, and shuttling through the lysosome and proteasome degradation pathways. Further understanding of how UV-PGE2-EP2 down-regulates E-cadherin may lead to novel chemopreventative strategies for the treatment of skin and other epithelial cancers.

Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness.

Ultraviolet (UV) light is a complete carcinogen inducing and promoting squamous-cell carcinoma (SCC) of the skin. Recent work has shown that SCC initiation and promotion are enhanced by prostaglandin E2 (PGE2). PGE2 interacts with specific EP receptors to regulate cellular functions. Previous work from our group has shown that the prostaglandin E2 EP2 receptor is a powerful regulator of keratinocyte growth. SKH-1 hairless mice lacking the EP2 receptor were therefore studied to understand how this growth signaling pathway contributes to photocarcinogenesis. Our data indicate that UV-irradiated mice lacking EP2 receptors exhibit decreased proliferation and a poor capacity for epidermal hypertrophy in response to UV injury. In a chronic irradiation model, these animals were protected from tumor formation, developing 50% fewer tumors than wild-type controls. Despite this capacity to protect against tumorigenesis, animals lacking EP2 receptors grew tumors that were larger in size, with a more aggressive phenotype. Further study suggested that this susceptibility may be associated with synthesis of active metalloproteinase enzymes in greater quantities than keratinocytes expressing the EP2 receptor, thereby enhancing the invasive potential of EP2-/- cells.