Genomics Inform.  2012 Sep;10(3):153-166. 10.5808/GI.2012.10.3.153.

Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling

• Krishnan J
• Choi S

• KMID: 1806244
• DOI: http://doi.org/10.5808/GI.2012.10.3.153

Abstract

A variety of ligands differ in their capacity to bind the receptor, elicit gene expression, and modulate physiological responses. Such receptors include Toll-like receptors (TLRs), which recognize various patterns of pathogens and lead to primary innate immune activation against invaders, and G-protein coupled receptors (GPCRs), whose interaction with their cognate ligands activates heterotrimeric G proteins and regulates specific downstream effectors, including immuno-stimulating molecules. Once TLRs are activated, they lead to the expression of hundreds of genes together and bridge the arm of innate and adaptive immune responses. We characterized the gene expression profile of Toll-like receptor 4 (TLR4) in RAW 264.7 cells when it bound with its ligand, 2-keto-3-deoxyoctonate (KDO), the active part of lipopolysaccharide. In addition, to determine the network communications among the TLR, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and GPCR, we tested RAW 264.7 cells with KDO, interferon-beta, or cAMP analog 8-Br. The ligands were also administered as a pair of double and triple combinations.

Keyword

gene expression; G-protein coupled receptors; immune responses; innate immunity; macrophages; Toll-like receptors

MeSH Terms

Arm
Gene Expression
GTP-Binding Proteins
Heterotrimeric GTP-Binding Proteins
Immunity, Innate
Interferon-beta
Ligands
Macrophages
Phosphotransferases
Sugar Acids
Toll-Like Receptor 4
Toll-Like Receptors
Transcriptome
Transducers
GTP-Binding Proteins
Heterotrimeric GTP-Binding Proteins
Interferon-beta
Ligands
Phosphotransferases
Sugar Acids
Toll-Like Receptor 4
Toll-Like Receptors