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A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide.

ABSTRACT: BACKGROUND: Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS) stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide. RESULTS: We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR. CONCLUSIONS: The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.

SUBMITTER: Paiva RT

PROVIDER: S-EPMC3434117 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide.

Paiva Renata T RT Saliba Alessandra M AM Fulco Tatiana O TO Sales Jorgenilce de Souza Jde S de Carvalho Daniel Serra DS Sampaio Elizabeth P EP Lopes Ulisses G UG Sarno Euzenir N EN Nobre Flavio F FF

BMC research notes 20120613

<h4>Background</h4>Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS) stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modu ...[more]

PMID: 22695124

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Project description:Although it is well known that neonatal sepsis can induce important alterations in cardiorespiratory control, their detailed early features and the mechanisms involved remain poorly understood. As a first step in resolving this issue, the main goal of this study was to characterize these alterations more extensively by setting up a full-term newborn lamb model of systemic inflammation using lipopolysaccharide (LPS) injection. Two 6-h polysomnographic recordings were performed on two consecutive days on eight full-term lambs: the first after an IV saline injection (control condition, CTRL); the second, after an IV injection of 2.5 μg/kg Escherichia coli LPS 0127:B8 (LPS condition). Rectal temperature, locomotor activity, state of alertness, arterial blood gases, respiratory frequency and heart rate, mean arterial blood pressure, apneas and cardiac decelerations, and heart-rate and respiratory-rate variability (HRV and RRV) were assessed. LPS injection decreased locomotor activity (p = 0.03) and active wakefulness (p = 0.01) compared to the CTRL. In addition, LPS injection led to a biphasic increase in rectal temperature (p = 0.01 at ∼30 and 180 min) and in respiratory frequency and heart rate (p = 0.0005 and 0.005, respectively), and to an increase in cardiac decelerations (p = 0.05). An overall decrease in HRV and RRV was also observed. Interestingly, the novel analysis of the representations of the horizontal and vertical visibility network yielded the most statistically significant alterations in HRV structure, suggesting its potential clinical importance for providing an earlier diagnosis of neonatal bacterial sepsis. A second goal was to assess whether the reflexivity of the autonomic nervous system was altered after LPS injection by studying the cardiorespiratory components of the laryngeal and pulmonary chemoreflexes. No difference was found. Lastly, preliminary results provide proof of principle that brainstem inflammation (increased IL-8 and TNF-α mRNA expression) can be shown 6 h after LPS injection. In conclusion, this full-term lamb model of systemic inflammation reproduces several important aspects of neonatal bacterial sepsis and paves the way for studies in preterm lambs aiming to assess both the effect of prematurity and the central neural mechanisms of cardiorespiratory control alterations observed during neonatal sepsis.

Dataset Information

A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide.

Publications

A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide.

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