Dataset Information

Motif prediction to distinguish LPS-stimulated pro-inflammatory vs. antibacterial macrophage genes.

ABSTRACT: BACKGROUND:Innate immunity is the first line of defence offered by host cells to infections. Macrophage cells involved in innate immunity are stimulated by lipopolysaccharide (LPS), found on bacterial cell surface, to express a complex array of gene products. Persistent LPS stimulation makes a macrophage tolerant to LPS with down regulation of inflammatory genes ("pro-inflammatory") while continually expressing genes to fight the bacterial infection ("antibacterial"). Interactions of transcription factors (TF) at their cognate TF binding sites (TFBS) on the expressed genes are important in transcriptional regulatory networks that control these pro-inflammatory and antibacterial expression paradigms involved in LPS stimulation. RESULTS:We used differential expression patterns in a public domain microarray data set from LPS-stimulated macrophages to identify 228 pro-inflammatory and 18 antibacterial genes. Employing three different motif search tools, we predicted respectively four and one statistically significant TF-TFBS interactions from the pro-inflammatory and antibacterial gene sets. The biological literature was utilized to identify target genes for the four pro-inflammatory profile TFs predicted from the three tools, and 18 of these target genes were observed to follow the pro-inflammatory expression pattern in the original microarray data. CONCLUSIONS:Our analysis distinguished pro-inflammatory vs. antibacterial transcriptomic signatures that classified their respective gene expression patterns and the corresponding TF-TFBS interactions in LPS-stimulated macrophages. By doing so, this study has attempted to characterize the temporal differences in gene expression associated with LPS tolerance, a major immune phenomenon implicated in various pathological disorders.

SUBMITTER: Kollipara RK

PROVIDER: S-EPMC2949756 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Motif prediction to distinguish LPS-stimulated pro-inflammatory vs. antibacterial macrophage genes.

Kollipara Rahul K RK Perumal Narayanan B NB

Immunome research 20100921

<h4>Background</h4>Innate immunity is the first line of defence offered by host cells to infections. Macrophage cells involved in innate immunity are stimulated by lipopolysaccharide (LPS), found on bacterial cell surface, to express a complex array of gene products. Persistent LPS stimulation makes a macrophage tolerant to LPS with down regulation of inflammatory genes ("pro-inflammatory") while continually expressing genes to fight the bacterial infection ("antibacterial"). Interactions of tra ...[more]

PMID: 20858252

Similar Datasets

Project description:Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may have therapeutic potential for neurodegenerative diseases by inhibiting inflammatory mediators and enhancing anti-inflammatory factor production in activated microglia.

Dataset Information

Motif prediction to distinguish LPS-stimulated pro-inflammatory vs. antibacterial macrophage genes.

Publications

Motif prediction to distinguish LPS-stimulated pro-inflammatory vs. antibacterial macrophage genes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets