title: The effect of acute and chronic photodamage on gene expression in human keratinocytes.
abstract: 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.
authors.affiliation: Department of Dermatology, UZ Sint Rafael, Catholic University of Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Garmyn
authors.forename: H
authors.initials: H
authors.lastname: Degreef
authors.forename: B A
authors.initials: BA
authors.lastname: Gilchrest
mesh_terms: D000328:Adult; D000368:Aged; D022762:CCAAT-Enhancer-Binding Proteins; D002478:Cells, Cultured; D055233:Cornified Envelope Proline-Rich Proteins; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000528:radiation effects*; D016762:Genes, fos / Q000528:radiation effects; D016259:Genes, myc / Q000528:radiation effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D015603:Keratinocytes / Q000528:radiation effects*; D008565:Membrane Proteins; D008875:Middle Aged; D011506:Proteins / Q000235:genetics; D011832:Radiation Injuries / Q000209:etiology / Q000235:genetics*; D012795:Sialoglycoproteins / Q000235:genetics; D015595:Skin Aging / Q000528:radiation effects; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D055233:Cornified Envelope Proline-Rich Proteins; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008565:Membrane Proteins; D011506:Proteins; D012795:Sialoglycoproteins; D014157:Transcription Factors; D051742:Transcription Factor CHOP