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The genetic basis of psoriasis has long been recognized, including the knowledge that family members of patients with psoriasis are at greater risk of developing the disease (Henselers and Christophers, 1995). Several lines of evidence suggest that genes regulating IL-12 and IL-23 may be important in its pathogenesis. Part of the rationale stems from observations indicating that patients with psoriasis and those with Crohn's disease share common features: patients with Crohn's disease are five times more likely than the general population to have psoriasis, and both diseases respond to anti-tumor necrosis factor-α therapy (Lee et al., 1990). A recent genome-wide association scan identified a highly significant association between Crohn's disease and a single-nucleotide polymorphism (SNP) in the coding region of the IL23R gene (Duerr et al., 2006), suggesting that this polymorphism might be present in patients with psoriasis. Additional studies from several diverse ethnic populations throughout the world have determined that psoriasis is associated with SNPs in IL-12 and IL-23 or their receptors (Capon et al., 2007; Cargill et al., 2007; Chang et al., 2007; Tsunemi et al., 2002).

Despite improvements in prevention and screening, mortality from advanced melanoma has not improved (Geller et al., 2007) and ultraviolet radiation (UV) is a major risk factor for melanoma development (Fears et al., 2002). Greater understanding of the mechanisms of melanoma development may lead to novel treatment options. As opposed to keratinocytes, which routinely undergo apoptosis after UVB irradiation, melanocytes resist apoptosis. In previous work, melanocytes and melanoma cells responded to UVB by activating an original pathway involving Gadd45a, one of the several growth-arrest and DNA damage–inducible genes (Lefort et al., 2001).

Non-melanoma skin cancer (NMSC) has been associated with several other conditions, including melanoma and non-Hodgkin's lymphoma (Hjalgri et al., 2000; Hu et al., 2005). In addition, the risk of NMSC has been found to be greater in various chronic disease groups (Frisch and Melbye, 1995; Frisch et al., 1996). It is uncertain whether this association is related to the treatments for those chronic diseases (such as radiation therapy or immunosuppressant therapy) rather than the disease itself (Karagas et al., 2001; Saladi and Persaud, 2005). Moreover, using a Danish nationwide cohort of patients with NMSC, Jensen et al. (2006) found a lower mortality in basal cell carcinoma (BCC) patients compared with the general population, reflecting what the authors suggested to be a selection bias to that data set.

Epithelia establish a microbial barrier against infection through the production of antimicrobial peptides (AMPs). In this study, we investigated whether catestatin (Cst), a peptide derived from the neuroendocrine protein chromogranin A (CHGA), is a functional AMP and is present in the epidermis. We show that Cst is antimicrobial against relevant skin microbes, including Gram-positive and Gram-negative bacteria, yeast, and fungi. The antimicrobial mechanism of Cst was found to be similar to other AMPs, as it was dependent on bacterial charge and growth conditions, and induced membrane disruption. The potential relevance of Cst against skin pathogens was supported by the observation that CHGA was expressed in keratinocytes. In human skin, CHGA was found to be proteolytically processed into the antimicrobial fragment Cst, thus enabling its AMP function. Furthermore, Cst expression in murine skin increased in response to injury and infection, providing potential for increased protection against infection. These data demonstrate that a neuroendocrine peptide has antimicrobial function against a wide assortment of skin pathogens and is upregulated upon injury, thus demonstrating a direct link between the neuroendocrine and cutaneous immune systems.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe mechanobullous disease characterized at the molecular level by mutations in the COL7A1 gene, leading to reduced type VII collagen and defective anchoring fibrils at the dermal–epidermal junction (DEJ) (Fine et al., 2000). Patients who inherit this condition suffer from recurrent blistering, cutaneous ulcers, severe scarring, and deformities, and they are at high risk for developing life-threatening squamous cell carcinoma (Mallipeddi, 2002). Currently, there is no treatment for RDEB.

Advances in phototherapy have led to significant improvement in the care of patients with a variety of skin disorders, ranging from psoriasis to vitiligo. The use of narrow-band ultraviolet radiation B (NB-UVB), with peak fluence at 311 nm, has been one such advance. Superior in efficacy to broad-band UVB (BB-UVB), it combines added efficacy similar to that of photochemotherapy (PUVA), with less inconvenience (van Weelden et al., 1988; Coven et al., 1997; Gathers et al., 2002). However, experimental data suggest that the use of NB-UVB is not without cost. Several investigative studies have determined that NB-UVB possesses greater potential for skin carcinogenesis (Flindt-Hansen et al., 1991; Wulf et al., 1994; Gibbs et al., 1995) than BB-UVB, already a known carcinogen (Kraemer, 1997).