Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of endotoxin-stimulated human monocytic cells in presence and absence of host defense peptide LL-37


ABSTRACT: The objective of the study was to evaluate transcriptional response of endotoxin-stimulated human monocytic cells in presence and absence of host defense peptide LL-37. A functional genomics approach was used to establish a temporal transcriptional profile and identify differentially expressed genes in LPS (100ng/ml)-stimulated human monocytic THP-1 cells, in the presence or absence of LL-37 (20ug/ml) after 1, 2, 4 and 24 hrs of stimulation. The peptide significantly inhibited the expression of LPS-induced pro-inflammatory genes regulated by NF-kappa B, such as NF-kappa B1 (p105/p50) and TNF-alpha-induced protein 2 (TNFAIP2). In contrast, LL-37 did not significantly inhibit LPS-induced genes that antagonize inflammation, such as TNF-alpha-induced protein 3 (TNFAIP3) and the NF-kappa B inhibitor, NF-kappa BIA, or genes involved in cell movement and recruitment (chemokines). The trends of gene expression were further validated by quantitative real-time PCR. This study implicates that LL-37 plays a role in the delicate balancing act of inflammatory responses.

ORGANISM(S): Homo sapiens

SUBMITTER: Neeloffer Mookherjee 

PROVIDER: E-FPMI-4 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37.

Mookherjee Neeloffer N   Brown Kelly L KL   Bowdish Dawn M E DM   Doria Silvana S   Falsafi Reza R   Hokamp Karsten K   Roche Fiona M FM   Mu Ruixia R   Doho Gregory H GH   Pistolic Jelena J   Powers Jon-Paul JP   Bryan Jenny J   Brinkman Fiona S L FS   Hancock Robert E W RE  

Journal of immunology (Baltimore, Md. : 1950) 20060201 4


The sole human cathelicidin peptide, LL-37, has been demonstrated to protect animals against endotoxemia/sepsis. Low, physiological concentrations of LL-37 (< or =1 microg/ml) were able to modulate inflammatory responses by inhibiting the release of the proinflammatory cytokine TNF-alpha in LPS-stimulated human monocytic cells. Microarray studies established a temporal transcriptional profile and identified differentially expressed genes in LPS-stimulated monocytes in the presence or absence of  ...[more]

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