Transcriptomics

Dataset Information

5

Monocyte vs Macrophage Study


ABSTRACT: Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages. Comparison of unstimulated monocytes and macrophages, and flagellin stimulated monocytes and macrophages.

ORGANISM(S): Homo sapiens  

SUBMITTER: Michael D George   William Hu  William K Hu 

PROVIDER: E-GEOD-22373 | ArrayExpress | 2010-07-07

SECONDARY ACCESSION(S): GSE22373PRJNA127653

REPOSITORIES: GEO, ArrayExpress

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Publications

Inflammation anergy in human intestinal macrophages is due to Smad-induced IkappaBalpha expression and NF-kappaB inactivation.

Smythies Lesley E LE   Shen Ruizhong R   Bimczok Diane D   Novak Lea L   Clements Ronald H RH   Eckhoff Devin E DE   Bouchard Phillipe P   George Michael D MD   Hu William K WK   Dandekar Satya S   Smith Phillip D PD  

The Journal of biological chemistry 20100413 25


Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins M  ...[more]

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