Lymphocyte-Derived Catecholamines Induce a Shift of Th1/Th2 Balance toward Th2 Polarization

Huang, Hua; Tang, Jian-Lei; Han, Xue; Peng, Yu‐Ping; Qiu, Yihua

doi:10.1159/000343099

Cited by 19 publications

(19 citation statements)

References 67 publications

(42 reference statements)

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“…These results reveal that TH gene overexpression in lymphocytes promotes a functional bias towards Th2 cells, suggesting that lymphocyte-derived CAs can promote Th cell function towards Th2 polarization. The present data extend our recent findings showing that α-methyl-p-tyrosine (α-MT), an inhibitor of TH, upregulates the expression of T-bet and IFN-γ, but downregulates the expression of GATA-3 and IL-4 in lymphocytes and that pargyline, an inhibitor of monoamine oxydase that degrades CAs, has the opposite effects to those of α-MT (22), supporting the viewpoint that lymphocyte-endogenous CAs regulate the Th1/Th2 balance and promote Th2 polarization. It has been reported that CAs derived from neurons and endocrine cells suppress the cellular immunity and shift the Th1/Th2 cytokine balance towards the Th2 profile (21,(27)(28)(29).…”

Section: Discussionsupporting

confidence: 89%

“…It has been reported that exogenous CAs can inhibit the secretion of pro-inflammatory cytokines and promote the release of anti-inflammatory cytokines (21). Although there is recent pharmacological evidence indicating that lymphocytederived CAs induce a shift in the Th1/Th2 balance toward Th2 polarization, that and α 1 -adrenoceptors (ARs) and β 2 -ARs are involved in mediating this effect (22,23), less is known about the role of the AR-coupled signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

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Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells

Huang

Zuo

Xiao

et al. 2016

International Journal of Molecular Medicine

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The aim of the present study was to examine the effect of the overexpression of tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of catecholamines (CAs), in lymphocytes on the differentiation and function of T helper (Th) cells. A recombinant TH overexpression plasmid (pEGFP-N1-TH) was constructed and transfected into mesenteric lymphocytes using nucleofection technology. These cells were stimulated with concanavalin A (Con A) for 48 h and then examined for TH expression and CA content, as well as for the percentage of Th1 and Th2 cells, cytokine concentrations and for the levels of signaling molecules. The lymphocytes overexpressing TH also expressed higher mRNA and protein levels of TH, and synthesized more CAs, including norepinephrine (NE), epinephrine (E) and dopamine (DA) than the mock-transfected control cells. TH gene overexpression in the lymphocytes reduced the percentage of interferon-γ (IFN-γ)-producing CD4+ cells and the ratio of CD4+IFN-γ+/CD4+IL-4+ cells, as well as the percentages of CD4+CD26+ and CD4+CD30+ cells and the ratio of CD4+CD26+/CD4+CD30+ cells. TH overexpression also reduced the secretion of IFN-γ and tumor necrosis factor (TNF) from lymphocytes. Moreover, NE inhibited the Con A-induced lymphocyte proliferation and decreased both cyclic adenosine monophosphate (cAMP) levels and p38 mitogen-activated protein kinase (MAPK) expression in the lymphocytes. Our findings thus indicate that TH gene overexpression promotes the polarization and differentiation of CD4+ cells towards Th2 cells, and this effect is mediated by the cAMP and p38 MAPK signaling pathways.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells

Huang

Zuo

Xiao

et al. 2016

International Journal of Molecular Medicine

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“…they have the enzyme tyrosine hydroxylase for the synthesis of CAs and the enzyme monoamine oxidase for the degradation of CAs [4,37,38,39,40,41]. Our recent study also showed that pargyline, an inhibitor of monoamine oxidase, increased dopamine, epinephrine and norepinephrine in both Con A-stimulated lymphocytes and in the supernatants of the lymphocyte cultures [10,22]. These findings provide a basis for the exploration of the mechanism endogenous CAs exert on lymphocyte differentiation using pargyline.…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous CAs can inhibit the secretion of proinflammatory cytokines and promote the release of anti-inflammatory cytokines [21]. We have recently demonstrated that endogenous CAs synthesized and secreted by lymphocytes induce a shift in the Th1/Th2 balance towards Th2 polarization [22]. Although endogenous CAs may exert their effects via an autocrine or/and paracrine pathway, the mechanism underlying endogenous CA-mediated Th differentiation remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Differentiation and Function of Helper T Cells by Lymphocyte-Derived Catecholamines via α<sub>1</sub>- and β<sub>2</sub>-Adrenoceptors

Huang¹,

Fang²,

Wang³

et al. 2014

Neuroimmunomodulation

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Objective: Recently, we have reported that lymphocyte-derived endogenous catecholamines (CAs) facilitate a shift in the T helper (Th)1/Th2 balance towards Th2. The purpose of this study was to explore the involvement of adrenoreceptors (ARs) in Th differentiation and function modulation by lymphocyte-derived CAs. Methods: Lymphocytes were separated from the mesenteric lymph nodes of mice, stimulated with concanavalin A (Con A) and treated with pargyline, an inhibitor of CA degradation. Results: Pargyline downregulated the expression of Th1-relative factors, T-bet, interferon (IFN)-γ and interleukin (IL)-2, but upregulated the expression of Th2-relative factors, GATA-3, IL-4 and IL-10. Pargyline reduced the percentage of IFN-γ-producing CD4+ cells and the CD4+IFN-γ+/CD4+IL-4+ cell ratio, although it did not alter the proportion of IL-4-producing CD4+ cells. In addition, the percentage of CD4+CD26+ T cells and the CD4+CD26+/CD4+CD30+ cell ratio were also reduced in the pargyline-treated group. Furthermore, Con A-activated T cells treated with pargyline produced a lower level of IFN-γ and a higher level of IL-4 than the control group. All these effects were blocked by the α₁-AR antagonist corynanthine or the β₂-AR antagonist ICI 118551, but not by the α₂-AR antagonist yohimbine or β₁-AR antagonist atenolol. Conclusions: These results imply that lymphocyte-derived CAs promote polarization of differentiation and function towards Th2 cells and that this effect is mediated by α₁-AR and β₂-AR.

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“…Huang et al investigated the effect of lymphocyte-derived catecholamines on the differentiation and function of T helper (Th) cells, suggesting that they shifted the Th1/Th2 balance in the direction of greater Th2 polarisation [154–155]. Panina-Bordignon et al had earlier suggested that beta2-adrenergic signalling inhibits production of IL-12, thereby promoting Th2 differentiation and inhibiting the Th1 development associated with anti-tumour immunity [156].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

Pantziarka

Bouche

Sukhatme³

et al. 2016

ecancer

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Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers.

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Lymphocyte-Derived Catecholamines Induce a Shift of Th1/Th2 Balance toward Th2 Polarization

Cited by 19 publications

References 67 publications

Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells

Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells

Regulation of Differentiation and Function of Helper T Cells by Lymphocyte-Derived Catecholamines via α<sub>1</sub>- and β<sub>2</sub>-Adrenoceptors

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

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