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Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model by Rafal Pawlinski, Brian Pedersen, Bettina Kehrle, William.

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Presentation on theme: "Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model by Rafal Pawlinski, Brian Pedersen, Bettina Kehrle, William."— Presentation transcript:

1 Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model by Rafal Pawlinski, Brian Pedersen, Bettina Kehrle, William C. Aird, Rolf D. Frank, Mausumee Guha, and Nigel Mackman Blood Volume 101(10):3940-3947 May 15, 2003 ©2003 by American Society of Hematology

2 LPS induction of Egr-1, PAI-1, ICAM-1, and TF mRNAs in the kidney.(A) Egr-1+/+ mice (2 per group) were either untreated (0 hours) or injected intraperitoneally with LPS (2 mg/kg) for various times (0.5 to 8 hours). Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology

3 LPS induction of TF, PAI-1, and ICAM-1 mRNA expression in the kidneys of Egr-1+/+ and Egr- 1−/− mice.(A-F) Egr-1+/+ and Egr-1−/− mice (3 or 4 per group) were either untreated or injected with LPS for either 3 or 8 hours. Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology

4 LPS induction of IL-6 and MCP-1 mRNA expression in the kidneys of Egr-1+/+ and Egr-1−/− mice.Egr-1+/+ and Egr-1−/− mice were either untreated (3 mice) or injected with LPS (4 mice per group) for either 3 or 8 hours. Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology

5 LPS induction of Egr-1 and TF chemokine expression in the lungs of Egr-1+/+ and Egr-1−/− mice.(A) (Left panel) Egr-1+/+ mice (2 per group) were either untreated (0 hours) or injected intraperitoneally with LPS (2 mg/kg) for various times (0.5 to 4 hours). Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology

6 Egr-1 and TF expression in the kidneys and lungs of untreated and LPS-treated mice.In situ hybridization experiments using an antisense Egr-1 riboprobe (A-C) detected Egr-1 mRNA expression in epithelial cells of distal tubules (A), urinary epithelium (B), a... Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology

7 LPS-induced inflammation in the lung and kidney.Lungs (A-F) and kidneys (G-I) from control (A,D,G), LPS-treated (8 hours) Egr-1+/+ (B,E,H), and LPS-treated (8 hours) Egr-1−/− (C,F,I) mice were stained with hematoxylin and eosin. Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology

8 LPS-induced inflammation in the lung.Leukocytes present in lungs from control (A), LPS-treated (8 hours) Egr-1+/+ (B), and LPS-treated (8 hours) Egr-1−/− (C) mice were stained with the napthol AS-D chloroacetate esterase reaction. Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology

9 LPS induction of inflammatory mediators in Egr-1+/+ and Egr-1−/− mice.Egr-1+/+ and Egr-1−/− mice (5 or 6 per group) were injected intraperitoneally with LPS (12 mg/kg) and serial blood samples were collected at various times. Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology

10 Survival of Egr-1+/+ and Egr-1−/− mice in a model of endotoxemia.Kaplan-Meier plots showing survival profiles of Egr-1+/+(n = 12, solid line) and Egr-1−/− (n = 10, dashed line) mice injected intraperitoneally with LPS (12 mg/kg). Rafal Pawlinski et al. Blood 2003;101:3940-3947 ©2003 by American Society of Hematology


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