Unknown,Transcriptomics,Genomics,Proteomics

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Transcription of Tnfaip3 is regulated by NF-kB and p38 via C/EBPβ in activated macrophages


ABSTRACT: Macrophages play a pivotal role in the immune system through recognition and elimination of microbial pathogens. Toll-like receptors (TLRs) on macrophages interact with microbial substances and initiate signal transduction through intracellular adapters. TLR4, which is important for the response to lipopolysaccharide (LPS), triggers downstream signaling mediators and eventually activates IkB kinase (IKK) complex and mitogen-activated protein kinases (MAPKs) such as p38. Previous reports revealed that, in addition to NF-kB, the induction of some LPS-inducible genes in macrophages required another transcription factor whose activity depends on p38. However, these transcription factors remained to be identified. Among these genes, NF-kB and C/EBPβ, a p38 downstream transcription factor, were predicted to co-regulate genes in LPS-stimulated BMDMs. Based on the subsequent results of a chromatin immunoprecipitation assay, we demonstrated that Tnfaip3 is regulated by both NF-kB and p38-dependent C/EBPβ. These results elucidate our understanding of the tight regulation of innate immunity. In order to identify p38-activated transcription factors that cooperate with NF-kB in response to LPS stimulation, microarrays were used to identify genes regulated by both NF-kB and p38 using wild-type, IKK-depleted, and p38 inhibitor-treated mouse bone marrow-derived macrophages (BMDMs). In silico analysis of transcription factor binding sites was used to predict the potential synergistic transcription factors from the co-expressed genes.

ORGANISM(S): Mus musculus

SUBMITTER: Mong-Hsun Tsai 

PROVIDER: E-GEOD-46361 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription of Tnfaip3 is regulated by NF-κB and p38 via C/EBPβ in activated macrophages.

Lai Ting-Yu TY   Wu Shang-Duen SD   Tsai Mong-Hsun MH   Chuang Eric Y EY   Chuang Li-Ling LL   Hsu Li-Chung LC   Lai Liang-Chuan LC  

PloS one 20130902 9


Macrophages play a pivotal role in the immune system through recognition and elimination of microbial pathogens. Toll-like receptors (TLRs) on macrophages interact with microbial substances and initiate signal transduction through intracellular adapters. TLR4, which recognizes the lipopolysaccharides (LPS) on Gram-positive and Gram-negative bacteria, triggers downstream signaling mediators and eventually activates IκB kinase (IKK) complex and mitogen-activated protein kinases (MAPKs) such as p38  ...[more]

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