Hindawi Publishing Corporation Journal of Biomedicine and Biotechnology Volume 2009, Article ID 193260, 12 pages doi:10.1155/2009/193260 Research Article Low-Frequency Low-Intensity Ultrasounds Do Not Influence the Survival and Immune Functions of Cultured Keratinocytes and Dendritic Cells Claudia Scarponi, 1 Francesca Nasorri, 1 Francesca Pavani, 2 Stefania Madonna, 1 Rosanna Sestito, 1 Marco Simonacci, 3 Ornella De Pit ` a, 1 Andrea Cavani, 1 and Cristina Albanesi 1 1 Laboratory of Immunology, Istituto Dermopatico dell’Immacolata (IDI)-IRCCS, Via Monti di Creta 104, 00167 Rome, Italy 2 Teuco Guzzini srl, Montelupone, 62010 Macerata, Italy 3 Unit` a Operativa di Dermatologia, Ospedale di Macerata, 62100 Macerata, Italy Correspondence should be addressed to Cristina Albanesi, c.albanesi@idi.it Received 27 April 2009; Revised 24 September 2009; Accepted 12 October 2009 Recommended by Ronald E. Baynes Low-frequency ultrasounds (US) are used to enhance drug transdermal transport. Although this phenomenon has been extensively analyzed, information on US effects on the single skin cell components is limited. Here, we investigated the possible effects of low- frequency US on viability and immune functions of cultured human keratinocytes and dendritic cells (DC), skin cells involved in the regulation of many immune-mediated dermatoses. We demonstrated that US, employed at low-frequency (42KHz) and low-intensity (0.15 W/cm 2 ) values known to enhance drug and water transdermal transport, did not affect extracellular-signal- regulated-kinase (ERK)1/2 activation, cell viability, or expression of adhesion molecules in cultured keratinocytes. Moreover, US at these work frequency and intensity did not influence the keratinocyte expression and release of immunomodulatory molecules. Similarly, cultured DC treated with low-frequency low-intensity US were viable, and did not show an altered membrane phenotype, cytokine profile, nor antigen presentation ability. However, intensity enhancement of low-frequency US to 5W/cm 2 determined an increase of the apoptotic rate of both keratinocytes and DC as well as keratinocyte CXCL8 release and ERK1/2 activation, and DC CD40 expression. Our study sustains the employment of low-frequency and low-intensity US for treatment of those immune skin disorders, where keratinocytes and DC have a pathogenetic role. Copyright © 2009 Claudia Scarponi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction Skin is a very efficient barrier against external agent penetra- tion. Low permeability is attributed to the stratum corneum, the outermost skin layer, characterized by a robust structure containing dense dead cells, corneocytes, which are embed- ded in a continuous matrix of lipid bilayers. The tightly packed stacks of lipid lamellae in the extracellular space make the stratum corneum a highly impermeable membrane [1]. Low permeability of the skin is also a limit for the transder- mal drug delivery, which could represent a valid alternative to oral delivery and injection. A diverse spectrum of mechanical [2, 3], electrical [4], and chemical [5] techniques have been previously explored to enhance skin permeability and, consequently, to increase the transdermal drug transport. Exposure to ultrasound (US) has also been shown to greatly enhance the permeability of skin for permitting transdermal drug delivery, a phenomenon termed sonophoresis [6–8]. Based on the frequency used, three types of US can be applied to increase skin permeability: therapeutic US (from 1 to 3 MHz), high-frequency US (above 3 MHz), and low- frequency US (20–100KHz). However, low-frequency US have been found to be more efficient than high-frequency US in inducing the transdermal transport [7, 8]. Previous studies have demonstrated that the generation of gas bubbles in the skin (cavitation) is the main mechanism responsible for sonophoresis and is better induced by low-frequency US, being inversely related to US frequency [9, 10]. The