The glucocorticoid inhibition of LFA-1 and CD2 expression by human mononuclear cells is reversed by IL-2, IL-7 and IL-15

Pipitone, Nicolò; Sinha, Monisha; Theodoridis, Efstathios; Goulding, N J; Hall, Marion H.; Lanchbury, Jerry S.; Corrigall, Valery; Panayi, G. S.; Pitzalis, Costantino

doi:10.1002/1521-4141(200107)31:7<2135::aid-immu2135>3.0.co;2-s

Cited by 16 publications

(14 citation statements)

References 25 publications

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“…38 At the cellular level, IL-7 has been implicated in modulating expression of surface adhesion molecules and chemokine receptors in vitro including CD11a expression. [39][40][41] Our data comparing relative expression levels of CD11a in naive T cells are evidence that short-term treatment with IL-7 may modulate CD11a expression in vivo. It remains a possibility that increased CD11a expression in naive cells and RTEs with rmIL-7 treatment may play an important role in the preferential trafficking of these For personal use only.…”

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confidence: 62%

Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function

Chu

Memon

Sharrow

et al. 2004

Blood

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Interleukin 7 (IL-7) is critical in maintaining thymic-dependent and thymic-independent pathways of T-cell homeostasis. T-cell receptor (TCR) rearrangement excision circles (TRECs) have been used as markers for recent thymic emigrants (RTEs) in assessing human thymic function. To study the thymic and peripheral effects of IL-7 on RTEs, we measured TREC content and peripheral naive T-cell subsets and turnover in IL-7-treated mice. Short-term administration of IL-7 into thymus-intact mice resulted in increased total TREC numbers, consistent with RTE accumulation. Decreases in TREC frequency were attributable to dilution secondary to increased cell turnover. Significantly, IL-7 administration into thymectomized mice resulted in patterns of decreased TREC frequency and increased total TREC number similar to those in IL-7-treated thymus-intact mice. Distinct patterns of naive cell and RTE distribution among peripheral immune organs and altered expression of CD11a were observed following IL-7 treatment in thymus-intact and thymectomized mice. These results demonstrate (1) that total TREC number and not TREC frequency accurately reflects quantitative changes in RTEs; (2) that short-term IL-7 administration results in preferential accumulations of RTEs among peripheral immune organs, accounting for the increase in TRECs in the total peripheral lymphoid pool; and IntroductionIdentifying factors regulating thymic function is critical in developing strategies to enhance and/or preserve immune function in immunodeficient states associated with HIV infection and hematopoietic stem cell transplantation (HSCT). An important parameter of thymic function is the generation of T cells as recent thymic emigrants (RTEs). In the absence of phenotypic markers distinguishing RTEs, measurement of T-cell receptor (TCR) rearrangement excision circles (TRECs) has been developed for quantifying RTEs in humans. 1 TRECs are episomal DNA circles generated during TCR rearrangement. Most human TCR␣/␤ ϩ T cells contain TRECs formed by the rearrangement between the ␦-rec and J␣ loci during TCR␦ locus deletion and TCR ␣Ϫchain gene rearrangement. 2 Because episomal DNA does not replicate, TREC frequency (ie, TREC molecules per cell number) decreases with successive cell divisions, permitting its use not only as a marker of thymic function, but also as a quantitative marker for RTEs in the periphery.Interpretation of human TREC data expressed as a frequency is problematic because this value can be influenced by changes in peripheral cell turnover in the absence of altered RTE generation. [3][4][5][6] Importantly, sampling of human tissue for TREC analysis is almost exclusively limited to the peripheral blood. Even when quantitatively expressed, TREC numbers in blood cannot detect changes in RTE trafficking among multiple lymphoid compartments and extra-lymphoid tissue, nor does it provide information regarding the maintenance of RTEs in these sites. Thus, changes in TREC frequency in many cases may not reflect thymic function, and measuring TRECs in...

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confidence: 62%

Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function

Chu

Memon

Sharrow

et al. 2004

Blood

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“…A number of studies mostly performed in immune cells reported that inflammatory cytokines can alter steroid cellular responses (36)(37)(38)(39). We recently provided the first demonstration that a similar phenomenon occurred in airway resident cells.…”

Section: Discussionmentioning

confidence: 87%

Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells

Tliba¹,

Damera²,

Banerjee³

et al. 2008

Am J Respir Cell Mol Biol

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We have previously shown that long-term treatment of airway smooth muscle (ASM) cells with a combination of TNF-a and IFN-g impaired steroid anti-inflammatory action through the up-regulation of glucocorticoid receptor beta isoform (GRb) (Mol Pharmacol 2006;69:588-596). We here found that steroid actions could also be suppressed by short-term exposure of ASM cells to TNF-a and IFN-g (6 h) as shown by the abrogated glucocorticoid responsive element (GRE)-dependent gene transcription; surprisingly, neither GRa nuclear translocation nor GRb expression was affected by cytokine mixture. The earlier induction of CD38, a molecule recently involved in asthma, seen with TNF-a and IFN-g combination but not with cytokine alone, was also completely insensitive to steroid pretreatment. Chromatin-immunoprecipitation (IP) and siRNA strategies revealed not only increased binding of interferon regulatory factor 1 (IRF-1) transcription factor to CD38 promoter, but also its implication in regulating CD38 gene transcription. Interestingly, the capacity of fluticasone to completely inhibit TNF-a-induced IRF-1 expression, IRF-1 DNA binding, and transactivation activities was completely lost in cells exposed to TNF-a and IFN-g in combination. This early steroid dysfunction seen with cytokine combination could be reproduced by enhancing IRF-1 cellular levels using constitutively active IRF-1, which dose-dependently inhibited GRE-dependent gene transcription. Consistently, reducing IRF-1 cellular levels using siRNA approach significantly restored steroid transactivation activities. Collectively, our findings demonstrate for the first time that IRF-1 is a novel alternative GRb-independent mechanism mediating steroid dysfunction induced by pro-asthmatic cytokines, in part via the suppression of GRa activities.

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“…Other studies in human peripheral blood mononuclear cells showed that the combination of IL-1␤, IL-6, and IFN␥ also decreased the suppressive action of dexamethasone on mitogen-induced proliferation (Almawi et al, 1991). In T cells, monocytes, and neutrophils, GC action is as well impaired when exposed to a single cytokine such as IL-2, IL-7, IL-13, IL-15, or IL-8 (Spahn et al, 1996;Pipitone et al, 2001;Strickland et al, 2001;Goleva et al, 2002). Although all in vitro studies describing GC insensitivity have been performed in either immune or transformed cells, very little is known about the modulation of GC signaling in structural cells that are relevant for lung diseases.…”

Section: Discussionmentioning

confidence: 99%

CD38 Expression Is Insensitive to Steroid Action in Cells Treated with Tumor Necrosis Factor-α and Interferon-γ by a Mechanism Involving the Up-Regulation of the Glucocorticoid Receptor β Isoform

Tliba

Cidlowski²,

Amrani³

2006

Molecular Pharmacology

100

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Evidence shows that the CD38 molecule, recently involved in the two main features of asthma, bronchial hyper-responsiveness and airway inflammation, could represent a new potential therapeutic target for asthma. In this study, we investigated whether glucocorticoid (GC), the most effective treatment for lung diseases, can affect CD38 expression in human airway smooth muscle (ASM) cells treated with different pro-inflammatory cytokines, such as tumor necrosis factor-␣ (TNF␣) and interferons (IFNs). We found that CD38 expression induced by TNF␣ alone was completely abrogated by fluticasone (100 nM), dexamethasone (1 M), or budesonide (100 nM). In contrast, the synergistic induction of CD38 by the combination of TNF␣ with IFN␥ or IFN␤, but not with IL-1␤ or IL-13, was completely insensitive to the GC inhibitory effects. We also found that TNF␣ and IFN␥ impaired GC responsiveness by inhibiting steroid induced both 1) GR␣-DNA binding activity and 2) GCresponsive element-(GRE)-dependent gene transcription. Although levels of the GC receptor (GR) ␣ isoform remained unchanged, expression of GR␤, the dominant-negative GR isoform, was synergistically increased by TNF␣ and IFN␥ with a GR␣/GR␤ ratio of 1 to 3. More importantly, fluticasone failed to induce GRE-dependent gene transcription and to suppress TNF␣-induced CD38 expression in ASM cells transfected with constitutively active GR␤. We conclude that, upon pro-inflammatory cytokine stimulation, CD38 expression becomes insensitive to GC action by a mechanism involving the up-regulation of GR␤ isoform, thus providing a novel in vitro cellular model to dissect GC resistance in primary cells.

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The glucocorticoid inhibition of LFA-1 and CD2 expression by human mononuclear cells is reversed by IL-2, IL-7 and IL-15

Cited by 16 publications

References 25 publications

Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function

Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function

Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells

CD38 Expression Is Insensitive to Steroid Action in Cells Treated with Tumor Necrosis Factor-α and Interferon-γ by a Mechanism Involving the Up-Regulation of the Glucocorticoid Receptor β Isoform

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