T CELL SUBSETS AND CYTOKINES IN ALLERGIC AND NON-ALLERGIC CHILDREN. I. ANALYSIS OF IL-4, IFN-γ AND IL-13 mRNA EXPRESSION AND PROTEIN PRODUCTION

Koning, H.; Neijens, H. J.; Baert, M.R.M.; Oranje, Arnold P.; Savelkoul, H.F.J.

doi:10.1006/cyto.1996.0184

Cited by 96 publications

(51 citation statements)

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“…The absolute amounts of IL-13 produced by submaximally stimulated T cells coincubated with LPA are within the range reported for activated T cells [i.e., on average a few hundred picograms per million T cells (9,11,28,38)]. In two out of five subjects, costimulation with LPA enhanced IL-13 secretion from baseline values that were below the level of detection (Fig.…”

Section: Lpa 1 and Lpa 2 Are Constitutively Expressed By Jurkat T Cellssupporting

confidence: 77%

Lysophosphatidic acid enhances interleukin-13 gene expression and promoter activity in T cells

Rubenfeld¹,

Guo²,

Sookrung³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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phosphatidic acid (LPA) is a membrane-derived lysophospholipid with wide-ranging effects on multiple lung cells including airway epithelial and smooth muscle cells. LPA can augment migration and cytokine synthesis in lymphocytes, but its potential effects on Th2 cytokines have not been well studied. We examined the effects of physiological concentrations of LPA on IL-13 gene expression in human T cells. The Jurkat T cell line and human peripheral blood CD4ϩ T cells were incubated with LPA alone or with 1) pharmacological agonists of different signaling pathways, or 2) antibodies directed against the T cell receptor complex and costimulatory molecules. Luciferase-based reporter constructs driven by different lengths of the human IL-13 promoter were transfected by electroporation in Jurkat cells treated with and without LPA. The effects of LPA on IL-13 mRNA stability were examined using actinomycin D to halt ongoing transcription. Expression of mRNA encoding LPA 2 and LPP-1 increased with T cell activation. LPA augmented IL-13 secretion under conditions of submaximal T cell activation. This was observed using pharmacological agonists activating intracellular calcium-, PKC-, and cAMP-dependent signaling pathways, as well as antibodies directed against CD3 and CD28. LPA only slightly prolonged IL-13 mRNA half-life in submaximally stimulated Jurkat cells. In contrast, LPA significantly enhanced transcriptional activation of the IL-13 promoter via regulatory elements contained within proximal 312 bp. The effects of LPA on IL-13 promoter activation appeared to be distinct from those mediated by GATA-3. LPA can augment IL-13 gene expression in T cells, especially under conditions of submaximal activation.T lymphocytes; transcription factors; inflammation; lysophospholipids; transcriptional regulation LYSOPHOSPHATIDIC ACID (LPA) is a lysophospholipid with farreaching effects on different cell types ranging from platelet activation to enhancing cell proliferation. LPA binds to several members of a family of G protein-coupled receptors including LPA 1 , LPA 2 , and LPA 3 (formerly known as endothelial differentiation gene or Edg receptor-2, -4, and -7, respectively). A fourth LPA receptor related to the purinergic receptor family was recently identified (37). LPA is detectable in normal serum at a concentration in the micromolar range, where it is bound by both albumin and gelsolin (33). Major sources of LPA include platelets, epithelial cells, and certain tumor cells (24).LPA is generated by the action of both secretory phospholipase A 2 (via hydrolysis of phosphatidic acid) and lysophopholipase D (via cleavage of extracellular lysophosphatidylcholine) on membrane phospholipids, with the latter pathway representing a potential pathway of cell activation in cancer (14,34).Although most studies to date have examined the effects of LPA on structural tissue cells such as endothelium and epithelium, emerging data suggest that LPA and related lysosphingolipids [e.g., sphingosine-1-phosphate (S1P)] activate circulating leukocyte...

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Section: Lpa 1 and Lpa 2 Are Constitutively Expressed By Jurkat T Cellssupporting

confidence: 77%

Lysophosphatidic acid enhances interleukin-13 gene expression and promoter activity in T cells

Rubenfeld¹,

Guo²,

Sookrung³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Peripheral blood monocytes from children and adults with asthma produce lower levels of IFN-g in response to allergen when compared with cells from control individuals (37,38). IFN-g levels are increased in allergic patients after immunotherapy (39,40).…”

Section: Discussionmentioning

confidence: 99%

IFN-γ Blocks Development of an Asthma Phenotype in Rhinovirus-Infected Baby Mice by Inhibiting Type 2 Innate Lymphoid Cells

Han

Hong

Jaipalli

et al. 2017

Am J Respir Cell Mol Biol

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Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of 6-day-old mice induces mucous metaplasia and airways hyperresponsiveness, which is dependent on IL-13, IL-25, and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-g expression, in contrast to mature 8-week-old mice with a robust IFN-g response, consistent with the notion that deficient IFN-g production in immature mice permits RV-induced type 2 immune responses. We therefore examined the effects of intranasal IFN-g administration on RVinduced ILC2 expansion and IL-13 expression in 6-day-old BALB/c and IL-13 reporter mice. Airway responses were assessed by histology, immunofluorescence microscopy, quantitative polymerase chain reaction, ELISA, and flow cytometry. Lung ILC2s were also treated with IFN-g ex vivo. We found that, compared with untreated RV-infected immature mice, IFN-g treatment attenuated RV-induced IL-13 and Muc5ac mRNA expression and mucous metaplasia. IFN-g also reduced ILC2 expansion and the percentage of IL-13-secreting ILC2s. IFN-g had no effect on the mRNA or protein expression of IL-25, IL-33, or thymic stromal lymphoprotein. Finally, IFN-g treatment of sorted ILC2s reduced IL-5, IL-13, IL-17RB, ST2, and GATA-3 mRNA expression. We conclude that, in immature mice, IFN-g inhibits ILC2 expansion and IL-13 expression in vivo and ex vivo, thereby attenuating RV-induced mucous metaplasia. These findings demonstrate the antagonistic function of IFN-g on ILC2 expansion and gene expression, the absence of which may contribute to the development of an asthma-like phenotype after early-life RV infection.

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“…On the other hand, it was undetectable in almost half of the subjects using our sensitive technique. At least 1 study 32 has suggested that elevated IL-4 mRNA production by peripheral blood T cells is a feature of child atopic, but not nonatopic asthma albeit after stimulation in vitro. Experiments with animal "models" of asthma typically involving ovalbumin sensitization and subsequent aerosol challenge of mice have also produced conflicting data on the possible roles of IL-4 and IL-5 in the pathogenesis of airway inflammation and hyperresponsiveness.…”

Section: Figmentioning

confidence: 99%

Expression of Activation Markers and Cytokine mRNA by Peripheral Blood CD4 and CD8 T Cells in Atopic and Nonatopic Childhood Asthma: Effect of Inhaled Glucocorticoid Therapy

et al. 2002

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ABSTRACT. Hypothesis. Activated CD8 as well as CD4 T cells contribute to the production of asthma-relevant cytokines in both atopic and nonatopic childhood asthma.Objectives. To measure the percentages of peripheral blood CD4 and CD8 T cells expressing naïve/memory (CD45RA/CD45RO) and activation (HLA-DR, CD25) markers, as well as mRNA-encoding interleukin-4 (IL-4) and interleukin-5 (IL-5) in atopic and nonatopic childhood asthmatics and in nonasthmatic controls matched for age and atopic status; and to study the effects of inhaled glucocorticoid therapy of the asthmatics on these measurements.Methods. Peripheral blood mononuclear cells were isolated from 17 atopic and 8 nonatopic stable (not acutely ill) asthmatics aged 7 to 16 years with moderateto-severe disease and from 15 nonasthmatic controls matched for age and atopic status. Activation markers on CD4 and CD8 T cells were measured by flow cytometry, and expression of cytokine mRNA by in situ hybridization with CD4 and CD8 T cells were isolated using magnetic beads. Measurements were repeated in 18 of the asthmatics 4 to 6 months after initiation or escalation of inhaled glucocorticoid therapy for inadequately controlled asthma.Results. The percentages of CD4 T cells expressing CD45RO but not CD45RA were elevated in both asthma groups as compared with the relevant controls and were reduced in association with de novo or augmented inhaled glucocorticoid therapy. The percentages of CD8 T cells expressing both markers were not elevated in asthmatics as compared with controls. The percentages of both CD4 and CD8 T lymphocytes expressing HLA-DR and CD25 were elevated in the asthmatics as compared with controls, and significantly reduced in association with de novo or augmented inhaled glucocorticoid therapy. ABBREVIATIONS. IL-5, interleukin 5; IL-4, interleukin 4; IgE, immunoglobulin E; FEV1, forced expiratory volume in 1 second; PEF, peak expiratory flow; FITC, fluoroscein isothiocyanate; PE, phycoerythrin; PBS, phosphate-buffered saline; NK, natural killer.

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T CELL SUBSETS AND CYTOKINES IN ALLERGIC AND NON-ALLERGIC CHILDREN. I. ANALYSIS OF IL-4, IFN-γ AND IL-13 mRNA EXPRESSION AND PROTEIN PRODUCTION

Cited by 96 publications

References 0 publications

Lysophosphatidic acid enhances interleukin-13 gene expression and promoter activity in T cells

Lysophosphatidic acid enhances interleukin-13 gene expression and promoter activity in T cells

IFN-γ Blocks Development of an Asthma Phenotype in Rhinovirus-Infected Baby Mice by Inhibiting Type 2 Innate Lymphoid Cells

Expression of Activation Markers and Cytokine mRNA by Peripheral Blood CD4 and CD8 T Cells in Atopic and Nonatopic Childhood Asthma: Effect of Inhaled Glucocorticoid Therapy

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