Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide

Li Jiang,Christine Røntved,Peter Sørensen,Klaus L Ingvartsen,Lotte Vels

doi:10.1186/1471-2164-9-443

Abstract

BackgroundLiver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli). To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM) exposure to E. coli lipopolysaccharide (LPS) treatment.ResultsApproximately 20% target transcripts were differentially expressed and eight co-expression clusters were identified. Each cluster had a unique time-dependent expression profile and consisted of genes involved in different biological processes. Our findings suggest that APR in the liver is triggered by the activation of signaling pathways that are involved with common and hepatic-specific transcription factors and pro-inflammatory cytokines. These mediators in turn stimulated or repressed the expression of genes encoding acute phase proteins (APP), collectins, complement components, chemokines, cell adhesion molecules and key metabolic enzymes during the APR. Hormones, anti-inflammatory and other hypothalamus-pituitary-adrenal axis (HPAA) linked mediators also seemed to participate in APR.ConclusionPerforming global gene expression analysis on liver tissue from IM LPS treated cows verified that the liver plays a major role in the APR of E. coli mastitis, and that the bovine hepatic APR follows the same pattern as other mammals when they are challenged with LPS. Our work presents the first insight into the dynamic changes in gene expression in the liver that influences the induction, kinetics and clinical outcome of the APR in dairy cows.

Highlights

Liver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli)
To gain a better insight into the genes and pathways involved in hepatic APR in dairy cows, we performed a global gene expression analysis of liver tissue sampled at different time points relative to intra-mammary exposure to LPS treatment
Of the 24128 target transcripts measured by the microarray approximately 20% were differentially expressed (DE) at one or more time points relative to LPS treatment

Summary

Introduction

Liver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli). Lipopolysaccharide (LPS) released from the cell wall of E. coli rapidly induces a sophisticated inflammatory response It is characterized by recruiting leukocytes especially neutrophils to the injured mammary tissue, as well as activation of macrophages in the mammary gland to produce pro-inflammatory cytokines [1]. LPS is a highly potent activator of the pro-inflammatory response during E. coli infection and is often used to simulate the gram negative mastitis. It provokes secretion of above pro-inflammatory cytokines which in turn activate or suppress expression of acute phase genes in hepatocytes, vascular endothelium and other target cells [2,3]. APR is commonly accompanied by a widespread change of metabolism [6]

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Discussion

Conclusion