title: Ultraviolet B radiation increases steady-state mRNA levels for cytokines and integrins in hairless mouse skin: modulation by topical tretinoin.
abstract: Chronically sun-damaged human skin has a wrinkled, aged appearance as a result of alterations in the dermal extracellular matrix. Secondary effectors such as cytokines and integrins may mediate the effects of UV radiation on the skin by regulating the synthesis of metalloproteinases and structural proteins including collagen. The aim of this study was to semi-quantify the steady-state mRNA levels of interleukin-1 alpha, tumor necrosis factor alpha, transforming growth factor beta, collagenase, stromelysin, collagen, and integrins (alpha, and alpha2) in the skin of hairless mice that were either treated with UV or concurrently treated with UV and topical tretinoin for 5 weeks. Total RNA was extracted from the skin of the mice, reverse transcribed to cDNA, and amplified by the polymerase chain reaction in the presence of 32P-dCTP using gene-specific primers. Results were normalized relative to glyceraldehyde-3-phosphate dehydrogenase levels. Steady-state mRNA levels of the cytokines and integrins were increased by UV radiation. Concurrent UV and topical tretinoin treatment superinduced the expression of interleukin-1, increased alpha 1, and decreased alpha 2 integrin expression. Immunofluorescence analysis showed increased dermal localization of beta 1 integrin in UV and tretinoin treated skin. These results suggest that cytokines and integrins may be involved in the mechanism of photo-damage.
authors.affiliation: Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: E
authors.initials: E
authors.lastname: Schwartz
authors.forename: A N
authors.initials: AN
authors.lastname: Sapadin
authors.forename: L H
authors.initials: LH
authors.lastname: Kligman
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003094:Collagen / Q000235:genetics; D017364:Collagenases / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D016023:Integrins / Q000235:genetics*; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007700:Kinetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D051379:Mice; D008812:Mice, Hairless; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D016023:Integrins; D007641:Keratolytic Agents; D012333:RNA, Messenger; D014212:Tretinoin; D003094:Collagen; D017364:Collagenases; D019278:Matrix Metalloproteinase 3