The effect of acute and chronic photodamage on gene expression in human keratinocytes.

We identified genes involved in the normal response to acute UV damage, as they were modulated in cultured newborn keratinocytes by a single sublethal UV dose, appropriately filtered to mimic solar radiation. Their gene products encode proteins involved in the regulation of cell growth (proto-oncogenes c-myc and c-fos), a gene inducible by growth arrest and DNA damage (GADD153), the cytokine interleukin (IL) 1 alpha and beta and finally a differentiation-associated small proline-rich gene (SPR2). Because chronically sun-exposed skin is known to have altered immune responsiveness and a statistical predisposition to skin cancer, we then examined UV induction of these genes in cultured keratinocytes derived from habitually sun-exposed adult skin, and for the older donors in paired cultures derived from sun-protected site of the same donors. Aging alone increased the baseline expression of two differentiation-associated genes (SPR2 and IL-1 receptor antagonist) in cultures from sun-protected skin. In contrast, photoaging increased the UV inducibility of c-fos but decreased the baseline expression of the differentiation-associated genes IL-1 receptor antagonist and SPR2.