Suppressors of Cytokine Signaling 3 Expression in Eosinophils: Regulation by PGE2and Th2 Cytokines

Esther López,Joaquín Sastre,Mar Fernández-Nieto,Victoria Del Pozo,Carlos Lahoz,María Paz Zafra,Beatriz Sastre,Santiago Quirce,Cristina Gámez

doi:10.1155/2011/917015

Abstract

Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E2 (PGE2) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/Th2 balance through SOCS3 production.

Highlights

Th2 respiratory disorders, such as asthma, allergic rhinitis, and nonasthmatic eosinophilic bronchitis (NAEB), have been major public health problems in the last two decades
Because it has been reported that prostaglandin E2 (PGE2) upregulates SOCS3 gene expression in different cell types, we examined the effect of PGE2 on SOCS3 expression in eosinophils from healthy subjects
Our results reveal that eosinophils are able to transcribe and express SOCS3 at the protein level, and this production is upregulated by IL-4, IL-5, IL-13, and PGE2

Summary

Introduction

Th2 respiratory disorders, such as asthma, allergic rhinitis, and nonasthmatic eosinophilic bronchitis (NAEB), have been major public health problems in the last two decades. NAEB was originally described by Gibson et al [1] and has subsequently been recognized as an important cause of chronic cough [2]. Asthma and NAEB are associated with a similar T-helper type 2 cytokine-driven airway inflammation [3, 4]. Airway hyperresponsiveness and variable airflow obstruction, which are the hallmarks of asthma, are not present in NAEB. Inflammatory mediators and cytokines play essential roles in the control of immune system; they act as growth factors, and regulate the differentiation, maintenance, and activation of naıve effectors and the memory state of immune cells [5]. The Th1/Th2 balance determines the nature of an immune response [6]; the mechanism by which Th1 and Th2 cytokines crossregulate the immune response remains unclear

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