Localization of substance P gene expression for evaluating protective countermeasures against sulfur mustard

Published on Nov 15, 2004in Toxicology4.221
· DOI :10.1016/J.TOX.2004.07.008
Stacy L. Casbohm5
Estimated H-index: 5
(Battelle Memorial Institute),
James V. Rogers16
Estimated H-index: 16
(Battelle Memorial Institute)
+ 5 AuthorsCarol L. K. Sabourin24
Estimated H-index: 24
(Battelle Memorial Institute)
Sources
Abstract
Abstract Sulfur mustard [bis(2-chloroethyl)sulfide; SM] is a chemical warfare agent that produces edema and blister formation with a severe inflammatory reaction. The mouse ear vesicant model for SM injury has been used to evaluate pharmacological agents for countering SM dermal injury. The vanilloid olvanil reduces SM-induced edema and mRNA expression of cytokines and chemokines, suggesting that blocking the inflammatory effects of neuropeptides, such as substance P (SP), may provide protection against SM-induced dermal injury. This study examined SP expression in mice exposed to SM (0.16 mg) on the inner surface of the right ear, with or without olvanil pretreatment at 1, 10, 30, 60, and 360 min following exposure. In naive skin, SP mRNA localization was associated with blood vessels and sebaceous glands. In SM-exposed skin, SP mRNA was also detected in perivascular dermal cells. Immunohistochemical localization of SP protein was observed in the ear skin of naive, SM-, olvanil/SM-, and vehicle-treated mice. Quantification of SP + perivascular dermal cells revealed that SM exposure led to a significant increase ( P ≤ 0.05) in SP + cells over the observed time period. Olvanil pretreatment significantly reduced ( P ≤ 0.05) the mean number of SP + cells at 60 and 360 min. This study demonstrates that SP expression could provide an additional endpoint for evaluating the effectiveness of vanilloid drugs on SM-induced skin inflammation.
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References28
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#1Michael C. Babin (Battelle Memorial Institute)H-Index: 13
#2Karen M. RickettsH-Index: 6
Last. Robert P. Casillas (Battelle Memorial Institute)H-Index: 20
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The mouse ear vesicant model (MEVM) is a screening tool used to identify protective compounds against acute sulfur mustard (SM)‐induced skin injury. It provides endpoints of edema and histopathology 24 h following a topical SM exposure to assess protection against inflammation and tissue damage. To further evaluate successful compounds, the MEVM was modified for use as a 7‐day model. Dose response studies were conducted with SM to select an optimal challenge dose for the new model. Due to severi...
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#1Carol L. K. Sabourin (Battelle Memorial Institute)H-Index: 24
#2Michele M. Danne (Battelle Memorial Institute)H-Index: 2
Last. Robert P. Casillas (United States Army Medical Research Institute of Chemical Defense)H-Index: 20
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Cutaneous exposure to sulfur mustard [bis(2-chloroethyl) sulfide (SM)] produces a delayed inflammatory skin response that is followed by severe dermal injury. Assessment of anti-inflammatory therapies against SM-induced skin injury has mainly relied on qualitative histopathological evaluation. The goal of this study was to identify proinflammatory biomarkers in the hairless mouse vesicant model that could be used as additional indicators of SM-induced skin injury for evaluating anti-inflammatory...
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#1Carol L. K. Sabourin (Battelle Memorial Institute)H-Index: 24
#2Michele M. Danne (Battelle Memorial Institute)H-Index: 2
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Cutaneous exposure to sulfur mustard [bis(2-chloroethyl) sulfide; SM] produces a delayed inflammatory skin response and severe tissue injury. Pig skin has organ similarities to human skin that is characterized by the content and types of epidermal lipids, the density of hair follicles and presence of sweat glands, which together afford penetration of topically applied compounds, complex inflammatory responses, and subsequent wound healing. The goal of this study was to identify in vivo proinflam...
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#1Robert P. Casillas (United States Army Medical Research Institute of Chemical Defense)H-Index: 20
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The mouse ear edema model is recognized for its usefulness in studying skin responses and damage following exposure to chemical irritants, and for evaluating pharmacological agents against chemically induced skin injury. We recently modified the mouse ear edema model for use with sulfur mustard (HD) and used this model to study the protective effect of 33 topically applied compounds comprising five pharmaceutical strategies (anti-inflammatories, protease inhibitors, scavengers/chelators, poly(AD...
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Cytokines play a major role in both acute and chronic inflammatory processes, including those produced by sulfur mustard (2,2′-dichlorodiethyl sulfide, HD). This study describes responses of normal human epidermal keratinocytes (NHEK) to HD, defined by interleukin-1β (IL-1β), IL-6, IL-8 and tumor necrosis factor alpha (TNF-α) release. Commercially available enzyme-linked immunosorbent assay (ELISA) kits were used to measure the cytokine release in NHEK during exposure to 100 and 300 μM of HD. Ex...
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The mouse ear vesicant model (MEVM) provides a quantitative edema response as well as histopathological and biochemical endpoints as measurements of inflammation and tissue damage following exposure to the chemical warfare agent sulfur mustard (HD). In the MEVM, several topically applied anti-inflammatory agents provided a significant degree of protection against HD-induced edema and dermal-epidermal separation. This study evaluated the protective effects of three of these pharmacological compou...
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#1James V. Rogers (Wright State University)H-Index: 7
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Intravenous injection of plasmid DNA encoding herpes simplex virus type-1 glycoprotein D (gD-1) complexed with asialoorosomucoid-poly-L-lysine (gD-ASOR) targets foreign DNA to the liver, leading to hepatic expression of gD-1. BALB/c mice were given two intravenous injections of gD-ASOR, pBK-ASOR (plasmid lacking the gD-1 gene but complexed with ASOR), or PBS. The skin was inoculated with 1 x 10 4 PFU of HSV-1 or sham-inoculated, and analyzed for infectious virus and cellular infiltration 1, 3, a...
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We have used tachykinin neurokinin-1 receptor (NK 1 receptor) knockout mice to learn of the link between NK 1 receptors and neutrophil accumulation in normal naive skin, as compared with inflamed skin. Intradermal substance P (300 pmol) induced edema formation in wild-type mice, but not in NK 1 knockout mice, as expected. However, in contrast to IL-1β (0.3 pmol), substance P did not induce neutrophil accumulation in wild-type mice. IL-1β-induced neutrophil accumulation was similar in wild-type a...
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#1Lester B. Lave (CMU: Carnegie Mellon University)H-Index: 58
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