A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide.
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.
Biomedical Engineering Program, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Renata T
RT
Paiva
Alessandra M
AM
Saliba
Tatiana O
TO
Fulco
Jorgenilce de Souza
Jde S
Sales
Daniel Serra
DS
de Carvalho
Elizabeth P
EP
Sampaio
Ulisses G
UG
Lopes
Euzenir N
EN
Sarno
Flavio F
FF
Nobre
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D019295:Computational Biology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013792:Thalidomide / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013792:Thalidomide