Cutaneous protease activity in the mouse ear vesicant model†

Powers, James C.; Kam, Chih-Min; Ricketts, Karen M.; Casillas, Robert P.

doi:10.1002/1099-1263(200012)20:1+<::aid-jat678>3.0.co;2-9

Cited by 16 publications

(10 citation statements)

References 16 publications

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“…Interestingly, our results may thus suggest that mast cells would play an important role in SMinduced microvesications, as mast cell degranulation and increase in MMP9 mRNA occur before the appearance of microvesications which are associated with the presence of neutrophils in fluid blisters. This hypothesis is concordant with previous reports showing a great increase of tryptase activity (Powers et al, 2000) and the preferential expression of MMP9 in skin (Shakarjian et al, 2006) after SM exposure in the mouse ear vesicant model.…”

Section: Discussionsupporting

confidence: 93%

“…Some studies have shown that SM exposure causes a significant reduction of the immunoreactivity of the latter protein (Greenberg et al, 2006;Smith et al, 1997bSmith et al, , 1998 which has been recently characterized by the degradation of the chain gamma-2 (Jin et al, 2008). In addition, some studies have suggested that proteases such as matrix metalloproteinases (MMP) are main players in SM-induced skin blister formation (Lindsay and Rice, 1995;Powers et al, 2000;Sabourin et al, 2002). Increases in MMP are of particular interest because of their ability to cleave basement membrane components and thus disrupt dermal/epidermal junction.…”

Section: Introductionmentioning

confidence: 99%

“…Several animal models including weanling pigs (Sabourin et al, 2002;Smith et al, 1996Smith et al, , 1997b, hairless guinea pig (Benson et al, 2011;Dachir et al, 2010Dachir et al, , 2012Smith et al, 1997a), rabbit (Dannenberg et al, 1985) or various mouse species (Lomash et al, 2011(Lomash et al, , 2013Powers et al, 2000;Ricketts et al, 2000;Sabourin et al, 2004;Wormser et al, 2005) have been used to investigate SMinduced skin toxicity. During the last years, the hairless mouse model stood out as the model of choice for studying the skin pathogenesis of SM Dorandeu et al, 2011;Joseph et al, 2011;Vallet et al, 2012) or its analogues the chloroethyl ethyl sulfide (CEES) (Jain et al, 2011a,b,b;Tewari-Singh et al, 2009) or the nitrogen mustard Jain et al, 2014;Tewari-Singh et al, 2013.…”

Section: Introductionmentioning

confidence: 99%

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Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

et al. 2015

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

et al. 2015

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“…Since this increase in MMP-9 correlates to increased tissue damage, it is hypothesized that a quantitative reduction of MMP-9 in skin would reduce the tissue damage normally observed after SM exposure. Studies have shown some success in the use of protease inhibitors both in vitro in cell culture (Cowan et al, 2000) and in an in vivo mouse model (Powers et al, 2000). It was tested whether or not topical skin treatment with MMP-2/MMP-9 inhibitor I [(2R)-2-[(4-Biphenylylsulfonyl)amino]-3-phenylpropionic acid (Fig.…”

Section: Introductionmentioning

confidence: 99%

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

Gerecke

Chen

Isukapalli

et al. 2009

Toxicology and Applied Pharmacology

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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 SMinduced 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.

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“…Of particular interest are our recent studies demonstrating that topical exposure of guinea pigs to the nitrogen mustard, mechlorethamine, induced skin MMP2, MMP3, and MMP9 activities (Wormser et al 2002a). Additionally, Powers et al (Powers et al 2000) have demonstrated increased levels of MMPs in mouse ear skin injured by SM, while a similar effect was observed by Sabourin et al (Sabourin et al 2002) in weanling pig skin model. Moreover, inhibition of matrix MMPs was shown to diminish the inflammatory response of mouse ear to the phorbol ester dibutyrate (Holleran et al 1997).…”

Section: Discussionmentioning

confidence: 63%

Protective effect of topical iodine containing anti-inflammatory drugs against sulfur mustard-induced skin lesions

Wormser

Sintov

Brodsky

et al. 2004

Archives of Toxicology

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Previous studies have shown the antidotal efficacy of topical iodine at 15 and 30 min post-exposure to sulfur mustard (SM). Here we demonstrate efficacy at longer intervals (20, 30, 45, and 60 min, respectively, for data) using an improved topical povidone-iodine preparation termed N66, which contains steroidal and non-steroidal anti-inflammatory agents. In the mouse, N66 reduced severity of ear edema by 43, 47, 44, and 36%; ear epidermal ulceration by 74, 58, 45, and 58%; and epidermal necrosis by 54, 34, 26, and 31% at the respective time points. A similar effect was observed with encrustation. The healing marker, grade of acanthotic area, showed dramatic increases of 39.6-, 25.3-, 20.9-, and 22-fold. Severity of the dermal parameters, acute inflammation and dermal necrosis, was reduced by 63, 34, 34, and 38% and 80, 54, 54, and 59%, respectively. In guinea pig skin, topical treatment with N66 45 min post-exposure reduced the SM-induced ulceration area by 75%. The histological parameters subepidermal microblister formation, epidermal ulceration, epidermal necrosis, and encrustation were reduced by 63, 61, 41, and 41%, respectively. The healing marker, grade of acanthotic area, was elevated by 73%. N66 induced a statistically significant reduction in two dermal markers for tissue damage: acute inflammation (33%) and dermal necrosis (48%). Reduced skin damage was also observed in areas adjacent the treated sites. The pharmacologically active components of N66 showed additive effect. These findings suggest that the povidone-iodine preparation combined with anti-inflammatory agents functions as a potent antidote against skin lesions induced by SM at relatively long intervals between exposure and treatment.

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Cutaneous protease activity in the mouse ear vesicant model†

Cited by 16 publications

References 16 publications

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

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

Protective effect of topical iodine containing anti-inflammatory drugs against sulfur mustard-induced skin lesions

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