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Title: Lipopolysaccharide-induced early response genes in bovine peripheral blood mononuclear cells implicate GLG1/E-selectin as a key ligand–receptor interaction

Author
item Li, Congjun - Cj
item Li, Robert
item Elsasser, Theodore
item Kahl, Stanislaw

Submitted to: Functional and Integrative Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/13/2009
Publication Date: 3/5/2009
Citation: Li, C., Li, R.W., Elsasser, T.H., Kahl, S. 2009. Lipopolysaccharide-induced early response genes in bovine peripheral blood mononuclear cells implicate GLG1/E-selectin as a key ligand–receptor interaction. Functional and Integrative Genomics. 9(3):335-349.

Interpretive Summary: LPS is an endotoxin produced by bacteria such as E. coli. LPS induces a strong response from normal animal immune systems during bacterial infection. To understand how an animal responds to the bacterial infection, we used a systems biology approach in order to study LPS-induced responses in animal (cattle) immune cells. Our results show that upon subjecting the immune cells to LPS, the cells become activated and start to proliferate. 464 genes, including 17 transcription factors, are induced by LPS. The analyses show that many functional networks, or regulatory pathways, are involved in the immune response. The activated transcription factors regulate the gene expression through potential interaction within the pathway networks. Functional analyses also revealed that LPS induces unique pathways, molecular functions, biological processes, and gene networks in animal immune cells. These data demonstrated that the transcriptional networks underlie immune cells’ specific transcription regulation and the response to pathogen components such as LPS.

Technical Abstract: This study uses a systems biology approach, integrating global gene expression information and knowledge of the regulatory events in cells to identify transcription networks controlling peripheral blood mononuclear cells’ (PBMCs) immune response to lipopolysaccharide (LPS) and to identify the molecular and cellular pathways’ responses to LPS. We identified that 464 genes, including at least 17 transcription factors, are significantly induced by two-hour LPS stimulation using a high density bovine microarray platform at a very stringent false discovery rate (FDR) = 0%. The networks show that in the LPS-stimulated PBMCs, altered gene expression was transcriptionally regulated via those transcription factors through potential interaction within the pathway networks. Functional analyses revealed that LPS induces unique pathways, molecular functions, biological processes, and gene networks. These data demonstrated that the transcriptional networks underlie PMBC-specific transcription regulation and the response to pathogen components such as LPS.