Tag: Distinct

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Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles.

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Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles.

J Allergy Clin Immunol. 2015 Apr 9;

Authors: Persson H, Kwon AT, Ramilowski JA, Silberberg G, Söderhäll C, Orsmark-Pietras C, Nordlund B, Konradsen JR, de Hoon MJ, Melén E, Hayashizaki Y, Hedlin G, Kere J, Daub CO

Abstract
BACKGROUND: Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA).
OBJECTIVE: We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes.
METHODS: Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs.
RESULTS: Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA), which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA.
CONCLUSION: Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.

PMID: 25863981 [PubMed – as supplied by publisher]

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Two distinct leukotriene B4 receptors, BLT1 and BLT2.

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Two distinct leukotriene B4 receptors, BLT1 and BLT2.

J Biochem. 2014 Dec 4;

Authors: Yokomizo T

Abstract
Leukotriene B4 (LTB4) is a potent inflammatory mediator derived from arachidonic acid. Two G protein-coupled receptors for LTB4 have been identified: a high-affinity receptor, BLT1, and a low-affinity receptor, BLT2. Both receptors mainly couple to pertussis toxin-sensitive Gi-like G proteins and induce cell migration. 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) was identified to bind BLT2 with higher affinity than LTB4. Expression of BLT1 was confirmed in type 1 helper T cells (Th1), Th2 cells, Th17 cells, effector CD8(+) T cells, dendritic cells, and osteoclasts in addition to granulocytes, eosinophils, and macrophages, and BLT1-deficient mice showed greatly reduced phenotypes in models of various inflammatory diseases, including peritonitis, bronchial asthma, rheumatoid arthritis, atherosclerosis, and osteoporosis. In mice, BLT2 expression is restricted to intestinal epithelial cells and epidermal keratinocytes. BLT2-deficient mice showed enhanced colitis after administration of dextran sulfate, possibly due to reduced intestinal barrier function. An aspirin-dependent reduction in 12-HHT production was responsible for delayed skin wound healing, showing that the 12-HHT/BLT2 axis also plays an important role in skin biology. BLT1 and BLT2 are therefore potential targets for the development of novel drugs.

PMID: 25480980 [PubMed – as supplied by publisher]

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Distinct Selectivity of Gangliosides Required for CD4(+) T and CD8(+) T Cell Activation.

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Distinct Selectivity of Gangliosides Required for CD4(+) T and CD8(+) T Cell Activation.

Biochim Biophys Acta. 2014 Sep 2;

Authors: Inokuchi JI, Nagafuku M, Ohno I, Suzuki A

Abstract
T cells compose a crucial part of the immune system and require activation. The first step of T cell activation is triggered by the movement of one of their surface molecules, known as T cell receptor, into localized regions of cell membrane known as lipid rafts. Molecules called gangliosides are known to be major components of lipid rafts, but their role in T-cell activation remains to be elucidated. This review summarizes recent findings that different types of T cells require distinct ganglioside types for the activation. Control of ganglioside expression would offer a strategy targeting for specific T-cell subpopulations to treat immune diseases. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics.

PMID: 25193136 [PubMed – as supplied by publisher]

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