Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

Environmental and Occupational Health Sciences Institute (EOHSI), a Joint Institute of UMDNJ-RW Johnson Medical School and Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Toxicology and Applied Pharmacology (Impact Factor: 3.63). 11/2008; 234(2):156-65. DOI: 10.1016/j.taap.2008.09.020
Source: PubMed

ABSTRACT Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Toxicogenomics enjoyed considerable attention as a ground-breaking addition to conventional toxicology assays at its inception. However, the pace at which toxicogenomics was expected to perform has been tempered in recent years. Next to cost the lack of advanced knowledge discovery and data mining tools significantly hampered progress in this new field of toxicological sciences. Recently, two of the largest toxicogenomics databases were made freely available to the public. These comprehensive studies are expected to stimulate knowledge discovery and development of novel data mining tools, which are essential to advance this field. In this review, we provide a concise summary of each of these two databases with a brief discussion on the commonalities and differences between them. We place our emphasis on some key questions in toxicogenomics and how these questions can be appropriately addressed with the two databases. Lastly, we provide a perspective on the future direction of toxicogenomics and how new technologies such as RNA-Seq may impact this field.
    Toxicological Sciences 07/2012; 130(2). DOI:10.1093/toxsci/kfs223 · 4.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chlorine is an industrial chemical that can cause cutaneous burns. Understanding the molecular mechanisms of tissue damage and wound healing is important for the selection and development of an effective post-exposure treatment. This study investigated the effect of cutaneous chlorine vapor exposure using a weanling swine burn model and microarray analysis. Ventral abdominal sites were exposed to a mean calculated chlorine vapor concentration of 2.9 g/L for 30 min. Skin samples were harvested at 1.5 h, 3 h, 6 h, and 24 h post-exposure and stored in RNAlater(®) until processing. Total RNA was isolated, processed, and hybridized to Affymetrix GeneChip(®) Porcine Genome Arrays. Differences in gene expression were observed with respect to sampling time. Ingenuity Pathways Analysis revealed seven common biological functions among the top ten functions of each time point, while canonical pathway analysis revealed 3 genes (IL-6, IL1A, and IL1B) were commonly shared among three significantly altered signaling pathways. The transcripts encoding all three genes were identified as common potential therapeutic targets for Phase II/III clinical trial, or FDA-approved drugs. The present study shows transcriptional profiling of cutaneous wounds induced by chlorine exposure identified potential targets for developing therapeutics against chlorine-induced skin injury.
    Cutaneous and Ocular Toxicology 04/2012; 31(4). DOI:10.3109/15569527.2012.679374 · 0.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate possible association between ophthalmic complications in sulfur mustard (SM) exposed patients with mild ocular injuries and serum soluble adhesion molecules. Serum levels of sICAM-1, sL-selectin, sP-selectin and sE-selectin in 367 SM-exposed individuals with or without eye injuries were checked and compared with 128 unexposed controls. All participants underwent ocular examinations. Serum sICAM-1 level in SM exposed with blurred vision, was significantly (p=0.021) higher than in SM exposed with no blurred vision. Serum sL-selectin level was significantly (p=0.024) higher in SM exposed with photophobia than SM exposed with no photophobia. Serum P-selectin level in exposed without any slit lamp findings was significantly (p=0.003) lower than the matched control groups. Similar finding was seen in exposed group without ocular problem compared with the control groups. Serum sE-selectin level in exposed with normal ocular condition except for photophobia and blurred vision was significantly (p<0.05) higher than the matched controls. Serum E-selectin level in exposed with photophobia condition was significantly (p=0.047) higher than the control group with photophobia. In conclusion it seems that the changes in the E- and P-selectins is a regulatory mechanism for inhibition of SM induced ocular problems, although the local levels are more important and further investigations required in more severe ocular problems in SM exposed patients.
    International immunopharmacology 01/2013; 17(3). DOI:10.1016/j.intimp.2012.12.014 · 2.71 Impact Factor

Full-text (2 Sources)

Available from
Jun 3, 2014