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Evaluation of gene expression in leukocytes of horses: analysis of the microarray technique in an ex vivo model of tolerance to endotoxin

Abstract

Endotoxemia is a clinical syndrome caused by the response to lipopolysaccharide (LPS) from Gram-negative bacteria. Usually this disease is associated with other diseases which affect the gastrointestinal tract of horses such as colic, intestinal inflammation and ischemia. Thus, changes in the intestinal wall contribute to the entry of LPS into the bloodstream of animals. The LPS induces an inflammatory response involving TLR-4 and 2, receptors CD4+, NF-kB, MyD88, IRAKs, TAK-1, TRAF-6, among other mediators. However, this cascade is altered when cells are exposed to subsequent LPS stimulation, leading to "endotoxin tolerance", characterized by cell anergy. But these changes do not follow a definite pattern. In a study of "endotoxin tolerance" in horses, using an ex vivo model, we observed a decrease in pro-inflammatory cytokines expression and increased expression of anti-inflammatory cytokines and cell surface expression of TLR-2 and 4. Therefore, a better understanding of the changes generated in the signaling pathways and mediators involved in this phenomenon is necessary. The objective of this study is to investigate changes in gene expression that trigger endotoxin tolerance in equine leukocytes using the technique of microarrays. (AU)

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