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

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. Bo...

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Bibliographic Details
Published in:Journal of applied toxicology 2006-05, Vol.26 (3), p.239-246
Main Authors: Shakarjian, Michael P., Bhatt, Pinaki, Gordon, Marion K., Chang, Yoke-Chen, Casbohm, Stacy L., Rudge, Thomas L., Kiser, Robyn C., Sabourin, Carol L., Casillas, Robert P., Ohman-Strickland, Pamela, Riley, David J., Gerecke, Donald R.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
blister
Blister - chemically induced
Blister - enzymology
Blister - pathology
Blotting, Western
Bullous diseases of the skin
chemical warfare
Chemical Warfare Agents - toxicity
Dermatology
gelatinase A
gelatinase B
Gene Expression - drug effects
Matrix Metalloproteinase 2 - biosynthesis
Matrix Metalloproteinase 9 - biosynthesis
Medical sciences
Mice
Mustard Gas - toxicity
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
skin
Skin - drug effects
Skin - enzymology
Skin - pathology
sulfur mustard
Toxicology
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Summary: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 m (0.08 mg) SM diluted in CH2Cl2. 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 (CH2Cl2 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. Copyright © 2006 John Wiley & Sons, Ltd.
ISSN:0260-437X
1099-1263
DOI:10.1002/jat.1134