Dataset Information

Inhibition of dendritic cell maturation and effector function

ABSTRACT: The initiation of donor derived dendritic cell (DC) adhesion and migration are one of the key events mediated by ischemia reperfusion injury (IRI) following solid organ transplantation. Recently we have been able to demonstrate that a single donor treatment with the synthetic metalloporphyrin cobalt protoporphyrin (CoPPIX) for heme oxygenase 1 (HO-1) induction results in the reduction of donor-derived DCs following IRI thus leading to the preservation of graft long-term function. Gene expression analysis in murine liver revealed the up-regulation of the signal transducer and activator of transcription 3 (STAT3) after CoPPIX treatment. Since it has been shown that CoPPIX is able to inhibit DC maturation, we could demonstrate that DC (-LPS) induced maturation guided by the secretion of pro-inflammatory cytokines and alloreactive T cell proliferation is dependent of STAT3 phosphorylation and independent of HO-1 activity. These observations highlight the immunomodulatory capacity of STAT3 which might be of further interest for the inhibition of immune response. Keywords: dendritic cells, heme oxygenase-1 (HO-1), STAT3, cobalt protoporphyrin

ORGANISM(S): Mus musculus

PROVIDER: GSE8452 | GEO | 2009/12/15

SECONDARY ACCESSION(S): PRJNA101531

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Invasion of cytotrophoblasts into uterine tissues is essential for placental development. To identify molecules regulating trophoblast invasion, mRNA signatures of purified villous (CTB, poor invasiveness) and extravillous (EVT, high invasiveness) trophoblasts isolated from first trimester human placentae and villous explant cultures, respectively, were compared using GeneChip analyses yielding 991 invasion/migration related transcripts. Several genes involved in physiological and pathologic cell invasion, including ADAM-12,-19,-28 as well as Spondin-2, were upregulated in EVT. Pathway prediction analyses identified several functional modules associated with either the invasive or the non-invasive trophoblast phenotype. One of the genes which were downregulated in the invasive mRNA pool, heme oxygenase-1 (HO-1), was selected for functional analyses. Real-time PCR analyses, Western blottting, and immunofluorescene of first trimester placentae and differentiating villous explant cultures demonstrated downregulation of HO-1 in invasive EVT as compared to CTB. Modulation of HO-1 expression in loss-of as well as gain-of function cell models (BeWo and HTR8/SVneo, respectively) demonstrated an inverse relationship of HO-1 expression with trophoblast migration in transwell and wound healing assays. Importantly, HO-1 expression led to an increase in protein levels and activity of the nuclear hormone receptor PPARgamma. Pharmacological inhibition of PPARgamma abrogated the inhibitory effects of HO-1 on trophoblast migration. Collectively, our results demonstrate that gene expression profiling of EVT and CTB can be used to unravel novel regulators of cell invasion. Accordingly, we identify heme oxygenase-1 as a negative regulator of trophoblast motility acting via upregulation of PPARgamma. Experiment Overall Design: To identify genes potentially regulating cell invasion trophoblast cells of early human gestation with distinct invasive properties were profiled. Experiment Overall Design: Distinct gene expression signatures of highly invasive EVT (n = 6) and poorly invasive CTB (n = 5) of different first trimester placentae using Affymetrix U133A GeneChips interrogating >20,000 genes were determined.

Dataset Information

Inhibition of dendritic cell maturation and effector function

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets