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2 results on '"Sandra J. Hoffman"'

1. Caspase-8 Collaborates with Caspase-11 to Drive Tissue Damage and Execution of Endotoxic Shock

Author

Shunsuke Otani, Eileen M. Burd, Scott B. Berger, Craig M. Coopersmith, Kristal M. Maner-Smith, John Bertin, Sandra J. Hoffman, Alexandra DeLaney, Gregory K. Tharp, Michelle C. Schaeffer, Linda Roback, Carol A. Capriotti, Peter J. Gough, Cedrick Young, Steven E. Bosinger, Zhe Liang, Nelson C. DiPaolo, Edward S. Mocarski, Dmitry M. Shayakhmetov, Igor E. Brodsky, Yanjun Feng, Pratyusha Mandal, John D. Lyons, and Eric A. Ortlund

Subjects
0301 basic medicine, Lipopolysaccharides, Male, Immunology, Apoptosis, Caspase-11, Caspase 8, Article, Proinflammatory cytokine, 03 medical and health sciences, RIPK1, 0302 clinical medicine, Intestine, Small, Immunology and Allergy, Animals, Kinase activity, Caspase, Cells, Cultured, Escherichia coli Infections, Inflammation, Mice, Knockout, biology, Tumor Necrosis Factor-alpha, Intracellular Signaling Peptides and Proteins, Interferon-beta, Phosphate-Binding Proteins, Shock, Septic, Caspases, Initiator, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Infectious Diseases, 030220 oncology & carcinogenesis, Caspases, Receptor-Interacting Protein Serine-Threonine Kinases, biology.protein, Tumor necrosis factor alpha, Female, Interferon Regulatory Factor-3, Apoptosis Regulatory Proteins, Spleen, Signal Transduction
Abstract

Summary The execution of shock following high dose E. coli lipopolysaccharide (LPS) or bacterial sepsis in mice required pro-apoptotic caspase-8 in addition to pro-pyroptotic caspase-11 and gasdermin D. Hematopoietic cells produced MyD88- and TRIF-dependent inflammatory cytokines sufficient to initiate shock without any contribution from caspase-8 or caspase-11. Both proteases had to be present to support tumor necrosis factor- and interferon-β-dependent tissue injury first observed in the small intestine and later in spleen and thymus. Caspase-11 enhanced the activation of caspase-8 and extrinsic cell death machinery within the lower small intestine. Neither caspase-8 nor caspase-11 was individually sufficient for shock. Both caspases collaborated to amplify inflammatory signals associated with tissue damage. Therefore, combined pyroptotic and apoptotic signaling mediated endotoxemia independently of RIPK1 kinase activity and RIPK3 function. These observations bring to light the relevance of tissue compartmentalization to disease processes in vivo where cytokines act in parallel to execute diverse cell death pathways.

Published
2018

2. Leucocyte cathepsin K affects atherosclerotic lesion composition and bone mineral density in low-density lipoprotein receptor deficient mice.

Author

Jian Guo, Ilze Bot, Ramon de Nooijer, Sandra J. Hoffman, George B. Stroup, Erik A.L. Biessen, G. Martin Benson, Pieter H.E. Groot, Miranda Van Eck, and Theo J.C. Van Berkel

Subjects
LEUCOCYTES, PROTEOLYTIC enzymes, ATHEROSCLEROSIS, BONE density, LOW density lipoproteins, LABORATORY mice, TARGETED drug delivery
Abstract

: Aims Cathepsin K (CatK), an established drug target for osteoporosis, has been reported to be upregulated in atherosclerotic lesions. Due to its proteolytic activity, CatK may influence the atherosclerotic lesion composition and stability. In this study, we investigated the potential role of leucocyte CatK in atherosclerotic plaque remodelling. : Methods and results To assess the biological role of leucocyte CatK, we used the technique of bone marrow transplantation to selectively disrupt CatK in the haematopoietic system. Total bone marrow progenitor cells from CatK+/+, CatK+/−, and CatK−/− mice were transplanted into X-ray irradiated low-density lipoprotein receptor knockout (LDLr−/−) mice. The selective silencing of leucocyte CatK resulted in phenotypic changes in bone formation with an increased total bone mineral density in the CatK−/− chimeras and an effect of gene dosage. The absence of leucocyte CatK resulted in dramatically decreased collagen and increased macrophage content of the atherosclerotic lesions while lesion size was not affected. The atherosclerotic lesions also demonstrated less elastic lamina fragmentation and a significant increase in the apoptotic and necrotic area in plaques of mice transplanted with CatK−/− bone marrow. : Conclusion Leucocyte CatK is an important determinant of atherosclerotic plaque composition, vulnerability, and bone remodelling, rendering CatK an attractive target for pharmaceutical modulation in atherosclerosis and osteoporosis. [ABSTRACT FROM AUTHOR]

Published
2009

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