Preferential expression of matrix metalloproteinase-9 in mouse skin after sulfur mustard exposure

Abstract

Matrix metalloproteinases (MMPs), a class of enzymes responsible for the degradation of extracellular matrix proteins, play important roles in inflammatory and immune responses. In skin, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are normally inactive but can be expressed during tissue injury. Both degrade collagen IV and other critical components of the basement membrane zone that separates the epidermis from the dermis. The expression of MMP-2 and -9 was studied in sulfur mustard (SM)-exposed ear skin from mice to determine their role in tissue vesicant injury. Punch biopsies of mouse ears were collected between 6 and 168 h after exposure to 97.5 mM (0.08 mg) SM diluted in CH(2)Cl(2). They were examined histologically and assayed for MMP-2 and -9 expression by gelatinase activity assays, real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. A time-related increase in overall gelatinase activity was observed in SM-treated ears. At 168 h after SM exposure, the relative levels of MMP-9 mRNA were increased 27-fold and MMP-9 protein 9-fold when compared with the control (CH(2)Cl(2) treated) ears. In contrast, there were no observable increases in the MMP-2 mRNA or protein levels between treated and control ears. These observations suggest the differential expression of MMP-2 and -9 during the cutaneous response to SM injury and suggest a role for MMP-9 in SM-induced injury.

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

“…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.…”

“…Increases in MMP are of particular interest because of their ability to cleave basement membrane components and thus disrupt dermal/epidermal junction. This is clearly illustrated by animal studies demonstrating an increase expression of mRNA and/ or protein levels for MMP-9 in SM-exposed skin Dachir et al, 2010;Sabourin et al, 2002;Shakarjian et al, 2006;Vallet et al, 2012).…”

Treatment of keratin intermediate filaments with sulfur mustard analogs

“…One hypothesis for vesicant action is the activation of an endogenous protease by SM [7][8][9][10] and an endogenous inhibitor of this protease has been identified [11,12]. Other investigators have analyzed the effects of SM on basal cell adhesion complex molecules [13][14][15][16][17], hypothesizing alkylation of basal cell adhesion complex molecules results in failure of the complex [16,18], leading to blister formation, similar to inherited skin blistering diseases [19].…”

Evaluation of relationship between the serum levels of inflammatory mediators and ocular injuries induced by sulfur mustard: Sardasht-Iran Cohort Study

“…Some in vitro and animal model studies have reported the association of acute SM complications with changes in MMP expression [29][30][31]. In a study on mice ear skin 7 days after exposure to SM, relative levels of MMP-9 mRNA and protein were increased 27-and 9-folds respectively compared to the control group [31].…”