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

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-prot...

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Main Authors: Jayalakshmi Krishnan, Sangdun Choi
Format: Article
Language:English
Published: BioMed Central 2012-09-01
Series:Genomics & Informatics
Subjects:
Online Access:http://genominfo.org/upload/pdf/gni-10-153.pdf
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author Jayalakshmi Krishnan
Sangdun Choi
author_facet Jayalakshmi Krishnan
Sangdun Choi
author_sort Jayalakshmi Krishnan
collection DOAJ
description 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-β, or cAMP analog 8-Br. The ligands were also administered as a pair of double and triple combinations.
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spelling doaj-art-4e0ab15cb61a4a428ed37372e6e262202025-02-02T04:29:26ZengBioMed CentralGenomics & Informatics1598-866X2234-07422012-09-0110315316610.5808/GI.2012.10.3.1539Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR SignalingJayalakshmi Krishnan0Sangdun Choi1Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.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-β, or cAMP analog 8-Br. The ligands were also administered as a pair of double and triple combinations.http://genominfo.org/upload/pdf/gni-10-153.pdfgene expressionG-protein coupled receptorsimmune responsesinnate immunitymacrophagesToll-like receptors
spellingShingle Jayalakshmi Krishnan
Sangdun Choi
Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling
Genomics & Informatics
gene expression
G-protein coupled receptors
immune responses
innate immunity
macrophages
Toll-like receptors
title Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling
title_full Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling
title_fullStr Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling
title_full_unstemmed Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling
title_short Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling
title_sort systems biological approaches reveal non additive responses and multiple crosstalk mechanisms between tlr and gpcr signaling
topic gene expression
G-protein coupled receptors
immune responses
innate immunity
macrophages
Toll-like receptors
url http://genominfo.org/upload/pdf/gni-10-153.pdf
work_keys_str_mv AT jayalakshmikrishnan systemsbiologicalapproachesrevealnonadditiveresponsesandmultiplecrosstalkmechanismsbetweentlrandgpcrsignaling
AT sangdunchoi systemsbiologicalapproachesrevealnonadditiveresponsesandmultiplecrosstalkmechanismsbetweentlrandgpcrsignaling