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Expression of cytokines and chemokines in mouse skin treated with sulfur mustard

TitleExpression of cytokines and chemokines in mouse skin treated with sulfur mustard
Publication TypeJournal Article
Year of Publication2018
AuthorsChang Y.C, Soriano M., Hahn R.A, Casillas R.P, Gordon M.K, Laskin J.D, Gerecke D.R
JournalToxicol Appl Pharmacol
Date PublishedSep 15
ISBN Number0041-008X (Linking)
Accession Number29935281
Keywords*Dermal toxicity, *Immuno-multiplex assays, *Inflammatory cells infiltration, *inflammatory mediators, *sulfur mustard, *Vesicants, Animals, Chemical Warfare Agents/*toxicity, Chemokines/*biosynthesis, Cytokines/*biosynthesis, Ear, External/drug effects/metabolism/pathology, Immunohistochemistry, Inflammation Mediators/metabolism, Inflammation/chemically induced/pathology, Male, Matrix Metalloproteinase 12/biosynthesis, Matrix Metalloproteinase 8/biosynthesis, Mice, Mustard Gas/*toxicity, RNA/biosynthesis/genetics, Skin Diseases/chemically induced/metabolism, Skin/*drug effects/*metabolism/pathology

Sulfur mustard (2,2'-dichlorodiethyl sulfide, SM) is a chemical warfare agent that generates an inflammatory response in the skin and causes severe tissue damage and blistering. In earlier studies, we identified cutaneous damage induced by SM in mouse ear skin including edema, erythema, epidermal hyperplasia and microblistering. The present work was focused on determining if SM-induced injury was associated with alterations in mRNA and protein expression of specific cytokines and chemokines in the ear skin. We found that SM caused an accumulation of macrophages and neutrophils in the tissue within one day which persisted for at least 7days. This was associated with a 2-15 fold increase in expression of the proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor alpha at time points up to 7days post-SM exposure. Marked increases (20-1000 fold) in expression of chemokines associated with recruitment and activation of macrophages were also noted in the tissue including growth-regulated oncogene alpha (GROalpha/CXCL1), monocyte chemoattractant protein 1 (MCP-1/CCL2), granulocyte-colony stimulating factor (GCSF/CSF3), macrophage inflammatory protein 1alpha (MIP1alpha/CCL3), and IFN-gamma-inducible protein 10 (IP10/CXCL10). The pattern of cytokines/chemokine expression was coordinate with expression of macrophage elastase/MMP12 and neutrophil collagenase/MMP8 suggesting that macrophages and neutrophils were, at least in part, a source of cytokines and chemokines. These data support the idea that inflammatory cell-derived mediators contribute to the pathogenesis of SM induced skin damage. Modulating the infiltration of inflammatory cells and reducing the expression of inflammatory mediators in the skin may be an important strategy for mitigating SM-induced cutaneous injury.

Short TitleExpression of cytokines and chemokines in mouse skin treated with sulfur mustard

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