Effect of Transmitters and Co-Transmitters of the Sympathetic Nervous System on Interleukin-6 Synthesis in Thymic Epithelial Cells

Patay, B. von; Kurz, Bodo; Mentlein, Rolf

doi:10.1159/000026363

Cited by 35 publications

(13 citation statements)

References 20 publications

(20 reference statements)

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“…Tracing analysis indicates that thymic sympathetic outflow directly starts in neurons from the thoracic spinal cord, brainstem, caudal raphe nucleus, and hypothalamus (Trotter et al, 2007). Furthermore, the neurotransmitter norepinephrine (Singh and Owen, 1976;Felten et al, 1987;Morale et al, 1992;Tsao et al, 1996;Kurz et al, 1997;von Patay et al, 1998von Patay et al, , 1999 is found in the thymus, and thymic cells express both ␤1-and ␤2-adrenergic receptors (Morale et al, 1992;Kurz et al, 1997;von Patay et al 1999) able to modulate maturation of T precursor cells and influence the thymic microenvironment. Thus, a link between the brain and the thymus is supported at different levels.…”

Section: Autonomic Denervation Of the Gld Thymusmentioning

confidence: 99%

Autonomic Denervation of Lymphoid Organs Leads to Epigenetic Immune Atrophy in a Mouse Model of Krabbe Disease

Galbiati¹,

Basso²,

Cantuti³

et al. 2007

J. Neurosci.

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Lysosomal ␤-galactosylceramidase deficiency results in demyelination and inflammation in the nervous system causing the neurological Krabbe disease. In the Twitcher mouse model of this disease, we found that neurological symptoms parallel progressive and severe lymphopenia. Although lymphopoiesis is normal before disease onset, primary and secondary lymphoid organs progressively degenerate afterward. This occurs despite preserved erythropoiesis and leads to severe peripheral lymphopenia caused by reduced numbers of T cell precursors and mature lymphocytes. Hematopoietic cell replacement experiments support the existence of an epigenetic factor in mutant mice reconcilable with a progressive loss of autonomic axons that hampers thymic functionality. We propose that degeneration of autonomic nerves leads to the irreversible thymic atrophy and loss of immune-competence. Our study describes a new aspect of Krabbe disease, placing patients at risk of immune-related pathologies, and identifies a novel target for therapeutic interventions.

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Section: Autonomic Denervation Of the Gld Thymusmentioning

confidence: 99%

Autonomic Denervation of Lymphoid Organs Leads to Epigenetic Immune Atrophy in a Mouse Model of Krabbe Disease

Galbiati¹,

Basso²,

Cantuti³

et al. 2007

J. Neurosci.

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“…TEC have been shown to synthesize various cytokines such as IL-1 and IL-6 [46]. von Patay et al [40] showed that NE stimulated IL-6 synthesis of TEC in vitro. Considering the finding that TEC express functional β-AR [21], various gene expressions including IL-6 in TEC would be regulated by stimulation of β-AR.…”

Section: Discussionmentioning

confidence: 99%

Effects of 6-Hydroxydopamine on the Development of the Immune System in Chickens.

Motobu

El-Abasy

et al. 2003

J. Vet. Med. Sci.

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ABSTRACT. It has been suggested that the sympathetic nervous system communicates with lymphocytes expressing cell surface receptors for neurotransmitters such as norepinephrine (NE), on the basis of the finding that neurotransmitters modify immune responses in mammalian species. We confirmed that chicken lymphocytes in the brusa of Fabricius, thymus and spleen expressed β-adrenergic receptor (β-AR) mRNA from embryonic day (E) 10 and that intracellular cAMP level was elevated by NE, suggesting that lymphocytes express functional β-AR on their surface at an early embryonal stage. To clarify whether the nervous system is involved in the development of the immune system, the effects of 6-hydroxydopamine (6-OHDA), one of sympathectomizing agents, on chicken lymphocytes was investigated. A single injection of 6-OHDA at a dose of 400 µg into a chicken embryo was carried out at E7 or 14 (as referred to E7 group and E14 group, respectively). NE level and the relative proportion of Bu-1a + , CD4 + and CD8 + cells in the spleen of 3-week-old chickens were not altered by 6-OHDA treatment. However, the proliferative responses and expression of IL-2 mRNA in spleen cells cultured with pokeweed mitogen were reduced in E7 group compared with those of control. Furthermore, in CD8 + spleen cells of E14 group of 3-week-old chickens, the expression of β-AR mRNA and the relative increase of intracellular cAMP stimulated with NE were significantly decreased. These results suggest that the sympathetic nervous system affects the development of the immune system. KEY WORDS: β-adrenergic receptor, cytokine, 6-hydroxydopamine, lymphocyte proliferation, norepinephrine.J. Vet. Med. Sci. 65(1): 35-42, 2003 It has been demonstrated that lymphoid organs, including the thymus, spleen and lymph nodes, are innervated by the sympathetic nervous system [9,45]. Norepinephrine (NE), a signaling molecule of the nervous system, is released from sympathetic nerve terminals and binds to high affinity β-adrenergic receptors (β-AR) that are expressed on various immune cells. β-AR transduce signals from NE to G protein, which in turn activates the adenylate cyclase to produce the second messenger cAMP. Stimulation of β-AR by NE has been reported to be associated with the cytokine production [35,36], cell proliferation [2], and the expression of surface molecules on immune cells [8,11,43].In the chicken, it is also observed that catecholamine modulates immune responses such as antibody responses [6,10], phytohemaglutinin wattle response and lymphocyte migration [31]. Denno et al. [6] showed that in vivo NE administration suppressed IgM-and IgG-PFC and in vitro NE treatment of spleen lymphocytes reduced IgM-PFC. This inhibition of IgM-PFC was blocked by treatment with antagonists to α-and β-receptors, suggesting that there are α-and β-receptor sites on lymphocytes and that catecholamine has a regulatory role in immunoglobulin synthesis.6-Hydroxydopamine (6-OHDA) is a neurotoxin that selectively destroys sympathetic nerve fibers with the catecholamine high a...

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“…It has been suggested that ATP released as a cotransmitter from sympathetic nerves leads to IL-6 production [576], implicating the presence of P2X7 receptors. Extracellular ATP induces phosphatidylserine externalisation earlier than nuclear apoptotic events in thymocytes [107].…”

Section: Thymusmentioning

confidence: 99%

Purinergic signalling in endocrine organs

Burnstock

2013

Purinergic Signalling

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There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5′-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors.

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Effect of Transmitters and Co-Transmitters of the Sympathetic Nervous System on Interleukin-6 Synthesis in Thymic Epithelial Cells

Cited by 35 publications

References 20 publications

Autonomic Denervation of Lymphoid Organs Leads to Epigenetic Immune Atrophy in a Mouse Model of Krabbe Disease

Autonomic Denervation of Lymphoid Organs Leads to Epigenetic Immune Atrophy in a Mouse Model of Krabbe Disease

Effects of 6-Hydroxydopamine on the Development of the Immune System in Chickens.

Purinergic signalling in endocrine organs

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