title: Transcriptional responses associated with sulfur mustard and thermal burns in porcine skin.
abstract: In military and civilian environments, serious cutaneous damage can result from thermal burns or exposure to the blistering agent sulfur mustard [bis (2-chloroethyl) sulfide; HD]. Similar therapies have historically been used to treat cutaneous thermal and HD injuries; however, the underlying molecular mechanisms of tissue damage and wound healing may differ between the types of burns. Using microarray analysis, this study assessed the transcriptional responses to cutaneous HD and thermal injury at 48 hours post-exposure to identify molecular networks and genes associated with each type of skin injury. Ventral abdominal sites on each of 4 weanling swine were exposed to 400 mul of undiluted HD or a heated brass rod (70 degrees C) for 8 minutes and 45-60 seconds, respectively. At 48 hours post-exposure, total RNA was isolated from excised skin samples and hybridized to Affymetrix GeneChip Porcine Genome Arrays (containing 20,201 genes). Both HD and thermal exposure promoted significant transcriptional changes where 290 and 267 transcripts were increased and 197 and 707 transcripts were decreased with HD and thermal exposure, respectively. HD- and thermal-injured skin expressed 149 increased and 148 decreased common transcripts. Comparison of the 10 most significantly changed biological functions for HD and thermal exposures identified 7 overlapping functional groups. Canonical pathways analysis revealed 15 separate signaling pathways containing transcripts associated with both HD and thermal exposure. Within these pathways, 5 transcripts (CXCR4, FGFR2, HMOX1, IL1R1, and TLR4) were identified as known targets for existing phase II/III clinical trial or Food and Drug Administration (FDA)-approved drugs. This study is the first to directly assess transcriptional changes in porcine skin subjected to HD or thermal injury over the same time period.
authors.affiliation: Battelle Memorial Institute, Biomedical Research Center, Columbus, Ohio 43201, USA. rogersjv@battelle.org
authors.forename: James V
authors.initials: JV
authors.lastname: Rogers
authors.forename: James N
authors.initials: JN
authors.lastname: McDougal
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Price
authors.forename: Frances M
authors.initials: FM
authors.lastname: Reid
authors.forename: John S
authors.initials: JS
authors.lastname: Graham
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006358:Hot Temperature; D009151:Mustard Gas / Q000633:toxicity*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D013552:Swine; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D012313:RNA; D009151:Mustard Gas