Beta-agonists modulate T-cell functions via direct actions on type 1 and type 2 cells

Loza, Matthew J.; Foster, Susan Leigh; Peters, Stephen P.; Penn, Raymond B.

doi:10.1182/blood-2005-08-3265

Cited by 67 publications

(77 citation statements)

References 71 publications

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“…Vasodilator-stimulated phosphoprotein (VASP) is a critical factor in regulating actin dynamics, and an increase in phospho-VASP is related to the increased levels of intracellular cAMP [4,10]. Treatment of B92 cells with IBMX and ISO increased phospho-VASP protein levels significantly in 10 min and slightly in 72 h compared with controls (Fig.…”

Section: Camp-stimulating Agents Promote Morphological Changesmentioning

confidence: 98%

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Activation of tumor suppressor protein PTEN and induction of apoptosis are involved in cAMP-mediated inhibition of cell number in B92 glial cells

Sugimoto¹,

Miwa²,

Ohno‐Shosaku³

et al. 2011

Neuroscience Letters

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Section: Camp-stimulating Agents Promote Morphological Changesmentioning

confidence: 98%

“…2-adrenoceptors, which are positively coupled to adenylate cyclase [10], and IBMX, which inhibits PDE, both increased intracellular cAMP levels. cAMP is therefore a prime candidate for the second messenger that is involved in the mechanisms changing cell morphology and function.…”

Section: Camp-stimulating Agents Promote Morphological Changesmentioning

confidence: 99%

Activation of tumor suppressor protein PTEN and induction of apoptosis are involved in cAMP-mediated inhibition of cell number in B92 glial cells

Sugimoto¹,

Miwa²,

Ohno‐Shosaku³

et al. 2011

Neuroscience Letters

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“…Formoterol also suppressed Df allergen-induced IFN-γ production of PBMCs in a dose-dependent manner [23]. Isoproterenol down-regulates IFN-γ mRNA expression of either concanavalin A (ConA)-stimulated or CD3-activated PBMCs [31] and inhibits IFN-γ production of PMA-stimulated peripheral blood lymphocytes (PBLs) [32]. …”

Section: Discussionmentioning

confidence: 99%

Salbutamol Modulates the Balance of Th1 and Th2 Cytokines by Mononuclear Cells from Allergic Asthmatics

Yamaguchi¹,

Soma²,

Takaku³

et al. 2010

Int Arch Allergy Immunol

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Background: There is evidence that excessive use of inhalational β₂-agonists induces the deterioration of asthma. Although the exact mechanism of this remains to be elucidated, overuse of β₂-agonists may impair the Th1/Th2 balance in asthmatic airways. The aim of the present study was to evaluate whether salbutamol, a representative inhalational β₂-agonist, modifies the production of Th1- and Th2-type cytokines by mononuclear cells separated from patients with asthma and healthy volunteers. Methods: Peripheral blood mononuclear cells (PBMCs) obtained from 8 healthy volunteers and 10 patients with mild persistent asthma allergic to house dust mites were treated with either salbutamol or medium alone. PBMCs were then stimulated with either medium alone, house dust mite (Dermatophagoides farina, Df) allergen or a combination of ionomycin plus phorbol 12-myristate 13-acetate ester (PMA). Concentrations of IFN-γ, IL-13, TNF-α and RANTES in the cell supernatants were measured using ELISA. Results: In PBMCs from healthy volunteers, salbutamol did not modify IFN-γ production, but increased the spontaneous production of IL-13. In contrast, salbutamol significantly inhibited the spontaneous and ionomycin- plus PMA-stimulated production of IFN-γ by PBMCs from asthmatics. Salbutamol significantly enhanced both spontaneous and Df-induced production of IL-13 by PBMCs from asthmatics. Salbutamol did not modify the production of TNF-α. Finally, salbutamol enhanced the production of RANTES induced by Df allergen in asthmatics. Conclusions: Salbutamol inhibits IFN-γ and enhances IL-13 production by PBMCs from asthmatics. These effects would promote a Th1/Th2 imbalance in the airways and may therefore contribute to the deterioration of asthma.

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“…However, various negative regulators of immunoreceptor signaling ensure that CD4 ϩ T cells either maintain the quiescent state of unstimulated, mature T cells or limit and terminate the activating signal, and therefore restore the dormant state of T cells (3,4). The second messenger cAMP has been recognized as an important mediator of such inhibitory signaling mechanisms by activation of the cAMP-protein kinase A (PKA), 3 with PKA functioning as a gatekeeper of tonic inhibition in T cells (5)(6)(7)(8)(9)(10).…”

Section: T He Cd4mentioning

confidence: 99%

Differential Expression and Function of Phosphodiesterase 4 (PDE4) Subtypes in Human Primary CD4+ T Cells: Predominant Role of PDE4D

Peter

Jin

Conti

et al. 2007

The Journal of Immunology

106

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Type 4 phosphodiesterases (PDE4) are critical regulators in TCR signaling by attenuating the negative constraint of cAMP. In this study, we show that anti-CD3/CD28 stimulation of human primary CD4+ T cells increases the expression of the PDE4 subtypes PDE4A, PDE4B, and PDE4D in a specific and time-dependent manner. PDE4A and PDE4D mRNAs as well as enzyme activities were up-regulated within 5 days, PDE4B showed a transient up-regulation with highest levels after 24 h. The induction was shown to be independent of different stimulation conditions and was similar in naive and memory T cell subpopulations. To elucidate the functional impact of individual PDE4 subtypes on T cell function, we used PDE4 subtype-specific short-interfering RNAs (siRNAs). Knockdown of either PDE4B or PDE4D inhibited IL-2 release 24 h after stimulation (time point of maximal IL-2 concentrations) to an extent similar to that observed with the panPDE4 inhibitor RP73401 (piclamilast). Substantial amounts of IFN-γ or IL-5 were measured only at later time points. siRNA targeting PDE4D showed a predominant inhibitory effect on these cytokines measured after 72 h. However, the inhibition of all cytokines was most effective when PDE4 siRNAs were applied in combination. Although the effect of PDE4 inhibition on T cell proliferation is small, the PDE4D-targeting siRNA alone was as effective as the panPDE4 inhibitor, whereas PDE4A or PDE4B siRNAs had hardly an effect. In summary, individual PDE4 subtypes have overall nonredundant, but complementary, time-dependent roles in propagating various T cell functions and PDE4D is the form likely playing a predominant role.

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Beta-agonists modulate T-cell functions via direct actions on type 1 and type 2 cells

Cited by 67 publications

References 71 publications

Activation of tumor suppressor protein PTEN and induction of apoptosis are involved in cAMP-mediated inhibition of cell number in B92 glial cells

Activation of tumor suppressor protein PTEN and induction of apoptosis are involved in cAMP-mediated inhibition of cell number in B92 glial cells

Salbutamol Modulates the Balance of Th1 and Th2 Cytokines by Mononuclear Cells from Allergic Asthmatics

Differential Expression and Function of Phosphodiesterase 4 (PDE4) Subtypes in Human Primary CD4+ T Cells: Predominant Role of PDE4D

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