Hannah R Cohen, Michelle A DeCourcey, William C Davis, Cleverson de Souza
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引用次数: 0
Abstract
Objective: The objective of this study was to investigate the differential expression of genes associated with coagulation in bovine monocyte-derived macrophages (MoMΦ) exposed to lipopolysaccharide (LPS) in vitro. We hypothesized that MoMΦ stimulated with LPS would have upregulation of procoagulant genes and downregulation of genes protecting against coagulation.
Methods: MoMΦ were isolated from Holstein steers and exposed to Escherichia coli-derived LPS or a control for 3 hours. We used transcriptomics (RNA sequencing) to characterize the differential expression of genes associated with coagulation in the LPS-exposed MoMΦ relative to the control group.
Results: 1,602 genes were upregulated and 1,209 genes downregulated 3 hours after exposure to LPS. Monocyte-derived macrophages exposed to LPS displayed statistically significant upregulation of 4 proinflammatory genes, 2 anti-inflammatory genes, 8 genes involved in promoting coagulation, and 5 genes considered protective against coagulation. There was significant downregulation of 1 gene involved in the promotion of coagulation.
Conclusions: Our results showed increased expression of most genes investigated promoting and protecting against coagulation and increased expression of proinflammatory and anti-inflammatory genes. These findings suggest that MoMΦ exhibit a multifaceted response in the early response to LPS, promoting and protecting against excessive coagulation. This multifaceted response highlights the interplay between different pathways involved in early sepsis.
Clinical relevance: Our data demonstrate the utility of using MoMΦ as a model system to investigate sepsis-associated coagulopathies. These insights into the early transcriptomic changes in response to LPS may help guide future research on the development of treatment modalities or diagnostic tests for patients with sepsis.
期刊介绍：
The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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