Temporal effects in porcine skin following bromine vapor exposure

Abstract

Bromine is an industrial chemical that causes severe cutaneous burns. When selecting or developing effective treatments for bromine burns, it is important to understand the molecular mechanisms of tissue damage and wound healing. This study investigated the effect of cutaneous bromine vapor exposure on gene expression using a weanling swine burn model by microarray analysis. Ventral abdominal sites were exposed to a mean calculated bromine vapor concentration of 0.51 g/L for 7 or 17 min. At 6 h, 48 h, and 7 days post-exposure, total RNA from skin samples was isolated, processed, and analyzed with Affymetrix GeneChip^® Porcine Genome Arrays (N = 3 per experimental group). Differences in gene expression were observed with respect to exposure duration and sampling time. Ingenuity Pathways Analysis (IPA) revealed four common biological functions (cancer, cellular movement, cell-to-cell signaling and interaction, and tissue development) among the top ten functions of each experimental group, while canonical pathway analysis revealed 9 genes (ARG2, CCR1, HMOX1, ATF2, IL-8, TIMP1, ESR1, HSPAIL, and SELE) that were commonly shared among four significantly altered signaling pathways. Among these, the transcripts encoding HMOX1 and ESR1 were identified using IPA as common potential therapeutic targets for Phase II/III clinical trial or FDA-approved drugs. The present study describes the transcriptional responses to cutaneous bromine vapor exposure identifying molecular networks and genes that could serve as targets for developing therapeutics for bromine-induced skin injury.

Keywords::

• Bromine
• skin
• porcine
• microarray

Acknowledgements

This work was conducted under DTRA/CBMS/MRMC Contract W81XWH-05-D-0001, Task Order 0010 with funding support through an Interagency Agreement (IAA) between the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) and National Institutes of Health, National Institute of Allergies and Infectious Disease (NIAID), IAA Number Y1-AI-6177-02. We thank James Mann, Amy Simmons, and Beth Reed for their excellent technical assistance. The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy, or decision unless so designated by other documentation. The experimental protocol was approved by the Animal Care and Use Committee at Battelle Memorial Institute and the US Army Medical Research and Materiel Command’s Animal Care and Use Review Office. All procedures were conducted in accordance with the principles stated in the Guide for the Care and Use of Laboratory Animals (National Research Council, 1996), and the Animal Welfare Act of 1966 (P.L. 89–544), as amended.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.