Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Difference of gene expression between LPS-stimulated monocytes cultured in the presence NRBCs and those cultured in the absence of NRBCs

ABSTRACT: We found that human cord blood nucleated red blood cells (NRBCs) have a regulatory function in the innate immune reaction. NRBCs suppressed the production of inflammatory cytokines including TNF-a and IL-1b from monocytes in response to lipopolysaccharide (LPS). NRBCs exerted the regulatory function even without cell-to-cell contact with monocytes. On the other hand, IL-10 production from monocytes by the stimulation of LPS in the presence of NRBCs was higher than that of LPS-stimulated monocytes cultured in the absence of NRBCs. Addition of an anti-IL-10 receptor blocking antibody restored the inflammatory cytokine production from monocytes, suggesting that the functional change of monocytes caused by the interaction of NRBCs was characterized and mediated by the increased IL-10 production. Whole-genome microarray analysis revealed that monocytes expressed increased amounts of IL-10 superfamily genes after the interaction with NRBCs. IL-19, one of the IL-10 superfamily, enhanced IL-10 production from monocytes, which suggested cooperative role of IL-10 superfamily in the suppression of inflammatory cytokine production from monocytes. Arginase which was reported to play an important role in the suppressive function of NRBCs on monocytes in mice was found to play no significant role in human monocytes. NRBCs seem to have a regulatory role to suppress vigorous innate immune reaction which can be harmful to the fetuses via some unknown soluble factor which enhances the production of IL-10 and IL-10 family cytokines in monocytes. Human LPS-stimulated monocytes were collected after culture in a condition without and with NRBCs in transwell culture system. Only one experiment was performed.

ORGANISM(S): Homo sapiens

SUBMITTER: Cui Li

PROVIDER: E-GEOD-70146 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Background: Therapeutic options capable of resolving inflammatory lung disease resulting from high-consequence occupational and environmental hazards are lacking. Objective: This study seeks to determine the therapeutic potential of direct lung-delivered interleukin (IL)-10 following repeated high concentration lipopolysaccharide exposures. Methods: C57BL/6 mice were intratracheally instilled with LPS (10μg) and then IL-10 (1μg) or vehicle (saline) control 5-hours later. This LPS exposure and treatment paradigm was then repeated daily for the next 2 days. Serum and lung tissues were collected and assessed for proinflammatory and profibrotic mediators. Lung cell infiltrates were enumerated by flow cytometry. Lung sections were stained for myeloperoxidase (MPO), CCR2, vimentin and post-translational protein citrullination (CIT) and malondialdehyde-acetaldehyde (MAA) modifications. Lung function testing and longitudinal in vivo micro-CT imaging were performed. Whole lungs were profiled using bulk RNA sequencing. Results: Repeated IL-10 therapy significantly (p<0.05) mitigated several LPS-induced adverse effects. IL-10 treatment reduced LPS-induced weight loss and serum pentraxin-2 and IL-6 levels. LPS-induced proinflammatory/profibrotic mediators (i.e., TNF-α, IL-6, CXCL1, CCL2, MMP-8, MMP-9, TIMP-1, fibronectin) were decreased with IL-10 treatment. IL-10 reduced LPS-induced influx of lung neutrophils, CD8+ T cells, NK cells, recruited monocyte-macrophages, and monocytes, as well as tissue expression of CCR2+ monocytes/macrophages, MPO+ neutrophils, vimentin, CIT, and MAA. IL-10 treatment reversed LPS-induced airway hyperresponsiveness. Micro-CT imaging confirmed reduction in LPS-induced lung density by IL-10 treatment. Lung-delivered IL-10 therapy administered after daily repeated endotoxin exposures strikingly reduces lung inflammatory and profibrotic processes and airway dysfunction to hasten lung recovery and resolution. Short-term, lung-localized IL-10 therapy following high-consequence environmental exposure events may represent a novel therapy to prevent chronic lung disease development.

Dataset Information

Difference of gene expression between LPS-stimulated monocytes cultured in the presence NRBCs and those cultured in the absence of NRBCs

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets