Common and specific signatures of gene expression and protein–protein interactions in autoimmune diseases

Autor: Tamir Tuller, Shimshi Atar, Asaf Achiron, Eytan Ruppin, M Gurevich
Rok vydání: 2012
Předmět:
Chemokine CXCL5
Chemokine CXCL6
Multiple Sclerosis
MAP Kinase Signaling System
Chemokine CXCL1
medicine.medical_treatment
Immunology
Gene Expression
Apoptosis
Biology
medicine.disease_cause
Calcitriol receptor
Autoimmune Diseases
Autoimmunity
Interferon-gamma
Crohn Disease
B-Cell Lymphoma 3 Protein
Interferon
Proto-Oncogene Proteins
Gene expression
Genetics
medicine
Humans
Lupus Erythematosus
Systemic
Protein Interaction Maps
Genetics (clinical)
Cell Proliferation
Inflammation
Lupus erythematosus
Receptors
IgE
Interleukin-8
Wnt signaling pathway
medicine.disease
Arthritis
Juvenile
Diabetes Mellitus
Type 1
Cytokine
Leukocytes
Mononuclear
Cancer research
Receptors
Calcitriol
Colitis
Ulcerative
Mitogen-Activated Protein Kinases
Signal transduction
Transcriptome
Chemokines
CXC
Signal Transduction
Transcription Factors
medicine.drug
Zdroj: Genes & Immunity. 14:67-82
ISSN: 1476-5470
1466-4879
DOI: 10.1038/gene.2012.55
Popis: The aim of this study is to understand intracellular regulatory mechanisms in peripheral blood mononuclear cells (PBMCs), which are either common to many autoimmune diseases or specific to some of them. We incorporated large-scale data such as protein-protein interactions, gene expression and demographical information of hundreds of patients and healthy subjects, related to six autoimmune diseases with available large-scale gene expression measurements: multiple sclerosis (MS), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), Crohn's disease (CD), ulcerative colitis (UC) and type 1 diabetes (T1D). These data were analyzed concurrently by statistical and systems biology approaches tailored for this purpose. We found that chemokines such as CXCL1-3, 5, 6 and the interleukin (IL) IL8 tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In addition, the anti-apoptotic gene BCL3, interferon-γ (IFNG), and the vitamin D receptor (VDR) gene physically interact with significantly many genes that tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In general, similar cellular processes tend to be differentially expressed in PBMC in the analyzed autoimmune diseases. Specifically, the cellular processes related to cell proliferation (for example, epidermal growth factor, platelet-derived growth factor, nuclear factor-κB, Wnt/β-catenin signaling, stress-activated protein kinase c-Jun NH2-terminal kinase), inflammatory response (for example, interleukins IL2 and IL6, the cytokine granulocyte-macrophage colony-stimulating factor and the B-cell receptor), general signaling cascades (for example, mitogen-activated protein kinase, extracellular signal-regulated kinase, p38 and TRK) and apoptosis are activated in most of the analyzed autoimmune diseases. However, our results suggest that in each of the analyzed diseases, apoptosis and chemotaxis are activated via different subsignaling pathways. Analyses of the expression levels of dozens of genes and the protein-protein interactions among them demonstrated that CD and UC have relatively similar gene expression signatures, whereas the gene expression signatures of T1D and JRA relatively differ from the signatures of the other autoimmune diseases. These diseases are the only ones activated via the Fcɛ pathway. The relevant genes and pathways reported in this study are discussed at length, and may be helpful in the diagnoses and understanding of autoimmunity and/or specific autoimmune diseases.
Databáze: OpenAIRE
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