Biomedical subjects

Olli Nevalainen

Publications and source records attributed to Olli Nevalainen.

5 recordsLinked to original sources

PubMed2003

Identification of novel genes regulated by IL-12, IL-4, or TGF-beta during the early polarization of CD4+ lymphocytes.

Th1 and Th2 cells arise from a common precursor cell in response to triggering through the TCR and cytokine receptors for IL-12 or IL-4. This leads to activation of complex signaling pathways, which are not known in detail. Disturbances in the balance between type 1 and type 2 responses can lead to certain immune-mediated diseases. Thus, it is important to understand how Th1 and Th2 cells are generated. To clarify the mechanisms as to how IL-12 and IL-4 induce Th1 and Th2 differentiation and how TGF-beta can inhibit this process, we have used oligonucleotide arrays to examine the early polarization of Th1 and Th2 cells in the presence and absence of TGF-beta. In addition to genes previously implicated in the process, we have identified 20 genes with various known and unknown functions not previously associated with Th1/2 polarization. We have also further determined which genes are targets of IL-12, IL-4, and TGF-beta regulation in the cells induced to polarize to Th1 and Th2 directions. Interestingly, a subset of the genes was coregulated by IL-12 or IL-4 and TGF-beta. Among these genes are candidates that may modulate the balance between Th1 and Th2 responses.

Biomarkers↗

PubMed2003

Identification of novel IL-4/Stat6-regulated genes in T lymphocytes.

IL-4, primarily produced by T cells, mast cells, and basophiles, is a cytokine which has pleiotropic effects on the immune system. IL-4 induces T cells to differentiate to Th2 cells and activated B lymphocytes to proliferate and to synthesize IgE and IgG1. IL-4 is particularly important for the development and perpetuation of asthma and allergy. Stat6 is the protein activated by signal transduction through the IL-4R, and studies with knockout mice demonstrate that Stat6 is critical for a number of IL-4-mediated functions including Th2 development and production of IgE. In the present study, novel IL-4- and Stat6-regulated genes were discovered by using Stat6(-/-) mice and Affymetrix oligonucleotide arrays. Genes regulated by IL-4 were identified by comparing the gene expression profile of the wild-type T cells induced to polarize to the Th2 direction (CD3/CD28 activation + IL-4) to gene expression profile of the cells induced to proliferate (CD3/CD28 activation alone). Stat6-regulated genes were identified by comparing the cells isolated from the wild-type and Stat6(-/-) mice; in this experiment the cells were induced to differentiate to the Th2 direction (CD3/CD28 activation + IL-4). Our study demonstrates that a number a novel genes are regulated by IL-4 through Stat6-dependent and -independent pathways. Moreover, elucidation of kinetics of gene expression at early stages of cell differentiation reveals several genes regulated rapidly during the process, suggesting their importance for the differentiation process.

Animals↗

PubMed2003

Kinetics and STAT4- or STAT6-mediated regulation of genes involved in lymphocyte polarization to Th1 and Th2 cells.

Many genes implicated in Th1 and Th2 differentiation have been identified in both human and mouse. However, the functional roles and hierarchy of these factors in the signaling pathways leading to either Th1 or Th2 responses are less clear. To explore at which stage of polarization the differences between Th1 and Th2 cells occur, we have studied the expression of 23 key genes implicated in the process during the first week of polarization from human precursor T helper cells using quantitative real-time reverse transcription-PCR. According to our results, 14 of the genes were clearly regulated differentially in Th1 and Th2 conditions in distinct time-dependent patterns, either during the first 2 days or after 1 week of polarization. Furthermore, 6 of these genes were identified to be targets of STAT4/6 regulation. Thus, for the first time we demonstrate expression kinetics of a number of key genes involved in Th1 and Th2 differentiation during the first week of polarization in both human and mouse. In addition, our study shows for the first time that the genes BCL-6 and TRADD are differentially regulated during the polarization of human Th1 and Th2 cells.

Animals↗

PubMed2003

Computational strategies for analyzing data in gene expression microarray experiments.

Microarray analysis has become a widely used method for generating gene expression data on a genomic scale. Microarrays have been enthusiastically applied in many fields of biological research, even though several open questions remain about the analysis of such data. A wide range of approaches are available for computational analysis, but no general consensus exists as to standard for microarray data analysis protocol. Consequently, the choice of data analysis technique is a crucial element depending both on the data and on the goals of the experiment. Therefore, basic understanding of bioinformatics is required for optimal experimental design and meaningful interpretation of the results. This review summarizes some of the common themes in DNA microarray data analysis, including data normalization and detection of differential expression. Algorithms are demonstrated by analyzing cDNA microarray data from an experiment monitoring gene expression in T helper cells. Several computational biology strategies, along with their relative merits, are overviewed and potential areas for additional research discussed. The goal of the review is to provide a computational framework for applying and evaluating such bioinformatics strategies. Solid knowledge of microarray informatics contributes to the implementation of more efficient computational protocols for the given data obtained through microarray experiments.

Algorithms↗

PubMed2002

Hierarchical grid transformation for image warping in the analysis of two-dimensional electrophoresis gels.

Two-dimensional electrophoresis is a widely used method for separating a large number of proteins from complex protein mixtures and for revealing differential patterns of protein expressions. In the computer-assisted proteome research, the comparison of protein separation profiles involves several heuristic steps, ranging from protein spot detection to matching of unknown spots. An important prerequisite for efficient protein spot matching is the image warping step, where the geometric relationship between the gel profiles is modeled on the basis of a given set of known corresponding spots, so-called landmarks, and the locations of unknown spots are predicted using the optimized model. Traditionally, polynomial functions together with least squares optimization has been used, even though this approach is known to be incapable of modeling all the complex distortions inherent in electrophoretic data. To satisfy the need of more flexible gel distortion correction, a hierarchical grid transformation method with stochastic optimization is presented. The method provides an adaptive multiresolution model between the gels, and good correction performance in the practical cross-validation tests suggests that automatic warping of gel images could be based on this approach. We believe that the proposed model also has significance in the ultimate comparison of corresponding protein spots since the matching process should benefit from the closeness of the true spot pairs.

Artifacts↗