Unknown,Transcriptomics,Genomics,Proteomics

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Suppression of LPS-induced IFNg and NO in splenocytes by select E2-regulated miRNA: A novel mechanism of immune mod.

ABSTRACT: microRNA (miRNA), recently identified, non-coding, small RNA, are emerging as key regulators in homeostasis of the immune system. Therefore, aberrant expression of miRNA may be linked to immune dysfunction, such as in chronic inflammation and autoimmunity. In this study, we investigated the potential role of miRNA in estrogen-mediated regulation of innate immune responses, as indicated by upregulation of LPS-induced IFNg, inducible nitric oxide synthase (iNOS), and nitric oxide in splenic lymphocytes from estrogen-treated mice. We found that miR-146a, a negative regulator of Toll-like receptor (TLR) signaling, was decreased in freshly-isolated splenic lymphocytes from estrogen-treated mice compared to placebo controls. Increasing the activity of miR-146a significantly inhibited LPS-induced IFNg and iNOS expression in mouse splenic lymphocytes. Further, miRNA microarray and Real-time RT-PCR analysis revealed that estrogen selectively upregulates/downregulates the expression of miRNA in mouse splenic lymphocytes. miR-223, which is highly upregulated by estrogen, regulates LPS-induced IFNg, but not iNOS or nitric oxide in splenic lymphocytes. Inhibition of miR-223 activity decreased LPS-induced IFNg in splenic lymphocytes from estrogen-treated mice. Our data are the first demonstrating selective regulation of miRNA expression in immune cells by estrogen and are indicative of an important role of miRNA in estrogen-mediated immune regulation. Keywords: microRNAs, estrogen, splenic lymphocytes, TLR4 signaling, mouse Total RNAs were isolated from freshly-isolated splenic lymphocytes from 2 pairs of placebo-and estrogen-treated mice

ORGANISM(S): Mus musculus

SUBMITTER: rujuan dai

PROVIDER: E-GEOD-11197 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation.

Dai Rujuan R Phillips Rebecca A RA Zhang Yan Y Khan Deena D Crasta Oswald O Ahmed S Ansar SA

Blood 20080912 12

MicroRNAs (miRNAs), recently identified noncoding small RNAs, are emerging as key regulators in homeostasis of the immune system. Therefore, aberrant expression of miRNAs may be linked to immune dysfunction, such as in chronic inflammation and autoimmunity. In this study, we investigated the potential role of miRNAs in estrogen-mediated regulation of innate immune responses, as indicated by up-regulation of lipopolysaccharide (LPS)-induced interferon-gamma (IFNgamma), inducible nitric oxide synt ...[more]

PMID: 18791161

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Project description:In the present study we analyzed miRNA and mRNA expression profiles in human peripheral blood lymphocytes (PBLs) incubated in microgravity condition, simulated by a ground-based Rotating Wall Vessel (RWV) bioreactor. Our results show that 42 miRNAs were differentially expressed in MMG-incubated PBLs compared with 1g-incubated ones. Among these, miR-9-5p, miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p were the most dysregulated. To improve the detection of functional miRNA-mRNA pairs we performed gene expression profiles on the same samples assayed for miRNA profiling and we integrated miRNA and mRNA expression data. The functional classification of miRNA-correlated genes evidenced significant enrichments in the biological processes of immune/inflammatory response, signal transduction, regulation of response to stress, regulation of programmed cell death and regulation of cell proliferation. We identified the correlation between miR-9-3p, miR-155-5p, miR-150-3p and miR-378-3p expression with that of genes involved in immune/inflammatory response (eg. IFNG and IL17F), apoptosis (eg. PDCD4 and PTEN) and cell proliferation (eg. NKX3-1 and GADD45A). Experimental assays of cell viability and apoptosis induction validated the results obtained by bioinformatics analyses demonstrating that in human PBLs the exposure to reduced gravitational force increases the frequency of apoptosis and decreases cell proliferation. microRNA expression profiling were carried out on total RNA extracted from PBLs of twelve healthy donors at the end of 24h-incubation time in MMG and in 1g conditions. Analyses were performed by using the M-bM-^@M-^\Human miRNA Microarray kit (V2)M-bM-^@M-^] (Agilent Technologies), that allows the detection of 723 known human (miRBase v.10.1) and 76 human viral miRNAs.By comparing the expression profile of MMG-incubated vs. 1g-incubated PBLs of the same donor, we found 42 differentially expressed miRNAs, 25 up-regulated and 17 down-regulated.

Dataset Information

Suppression of LPS-induced IFNg and NO in splenocytes by select E2-regulated miRNA: A novel mechanism of immune mod.

Publications

Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation.

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