記事の詳細

36回日本臨床免疫学会総会抄録集
セッションID: 2-47

http://doi.org/10.14906/jscisho.36.0.162.0
主催: 日本臨床免疫学会

Network-based Analysis of Immune Response-Related Genes Expressed in Systemic Lupus Erythematosus - An Interaction among Type I and Type II Interferon, Tumor Necrosis Factor, and Beta-estradiol-
*李 慧敏1), 美馬 亨1), 杉野 英彦1),青木 千恵子1), 安達 康雄1), 吉雄 直子1), 松原 謙一2), 西本 憲弘1)
1) 大阪大学大学院生命機能研究科免疫制御学講座 2) DNAチップ研究所
公開日 2008/10/06

キーワード: systemic lupus erythematosus, DNA microarray, network-based analysis, interferon, tumor necrosis factor

Abstract (抄録)

Objective. To investigate the interaction of immune response-related molecules expressed in peripheral blood of SLE patients. Method. Gene expression profiles of peripheral bloods from SLE patients and healthy women were analyzed by DNA microarray. Differentially expressed genes related to immune response were selected and analyzed by network-based analysis. To investigate the interactions among TNF, IFNγ, beta-estradiol (E2), and IFNα on interferon-inducible (IFI) genes, we carried out stimulating and co-stimulating experiments on PBMCs followed by real-time PCR. Results. Overexpressed IFI genes were confirmed. Several networks, which included cytokines such as TNF and IFNγ, or E2, were constructed by network-based analysis on the immune response-related genes. TNF-regulated genes were dominant in these networks but TNF stimulating experiment on PBMCs showed no different responses to TNF between SLE and healthy donors in vitro. Co-stimulating experiments by TNF, IFNγ, and E2 with IFNα revealed that TNF has repressive while IFNγ essentially has synergistic effect with IFNα on IFI genes in PBMC in vitro. E2 showed different effects on some IFI genes among 3 healthy donors.Conclusions. Functional interactions among immune response-related molecules were found. Cross-regulations among TNF, IFNγ, E2, and IFNα were suggested involving in the pathogenesis of SLE.

リンク先
http://jsci.imic.or.jp/36soukai.html

参考文献
http://www.ncbi.nlm.nih.gov/pubmed/19121222

Arthritis Res Ther.

2009;11(1):R1. doi: 10.1186/ar2584. Epub 2009 Jan 3.
Interactions among type I and type II interferon, tumor necrosis factor, and beta-estradiol in the regulation of immune response-related gene expressions in systemic lupus erythematosus.
Lee HM1, Mima T, Sugino S(杉野英彦), Aoki C, Adachi Y, Yoshio-Hoshino N,
Matsubara K, Nishimoto N.

Author information
1Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University,1-3 Yamada-Oka, Suita City, Osaka 565-0871, Japan.

INTRODUCTION:
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by various clinical manifestations. Several cytokines interact and play pathological roles in SLE, although the etiopathology is still obscure. In the present study we investigated the network of immune response-related molecules expressed in the peripheral blood of SLE patients, and the effects of cytokine interactions on the regulation of these molecules.

METHODS:
Gene expression profiles of peripheral blood from SLE patients and from healthy women were analyzed using DNA microarray analysis. Differentially expressed genes classified into the immune response category were selected and analyzed using bioinformatics tools. Since interactions among TNF, IFNgamma, beta-estradiol (E2), and IFNalpha may regulate the expression of interferon-inducible (IFI) genes, stimulating and co-stimulating experiments were carried out on peripheral blood mononuclear cells followed by analysis using quantitative RT-PCR.

RESULTS:
Thirty-eight downregulated genes and 68 upregulated genes were identified in the functional category of immune response. Overexpressed IFI genes were confirmed in SLE patient peripheral bloods. Using network-based analysis on these genes, several networks including cytokines--such as TNF and IFNgamma--and E2 were constructed. TNF-regulated genes were dominant in these networks, but in vitro TNF stimulation on peripheral blood mononuclear cells showed no differences in the above gene expressions between SLE and healthy individuals. Co-stimulating with IFNalpha and one of TNF, IFNgamma, or E2 revealed that TNF has repressive effects while IFNgamma essentially has synergistic effects on IFI gene expressions in vitro. E2 showed variable effects on IFI gene expressions among three individuals.

CONCLUSIONS:
TNF may repress the abnormal regulation by IFNalpha in SLE while IFNgamma may have a synergistic effect. Interactions between IFNalpha and one of TNF, IFNgamma, or E2 appear to be involved in the pathogenesis of SLE.
PMID:19121222

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