Adenosine Increases Interleukin 6 Release and Decreases Tumour Necrosis Factor Release From Rat Adrenal Zona Glomerulosa Cells, Ovarian Cells, Anterior Pituitary Cells and Peritoneal Macrophages

Ritchie, Paul K.; Spangelo, Bryan L.; Krzymowski, David K.; Rossiter, Tamra B.; Kurth, E. J.; Judd, Allan M.

doi:10.1006/cyto.1996.0153

Cited by 54 publications

(30 citation statements)

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“…We observe decreased LPS-induced TNF-a mRNA levels as a result of NECA stimulation, which is consistent with previous studies (1). We also show that NECA has the capacity to further enhance LPSstimulated IL-6 gene expression, consistent with responses in peritoneal macrophage cells (35). Screening reveals that NECA treatment of LPS-primed monocytes results in the modulation of genes involved in immune cell chemotaxis (CCR1 and CCR4) and T cell activation (IL-23p19; Fig.…”

Section: Nr4a2 and Nr4a3 Regulate Macrophage Inflammatory Gene Expressupporting

confidence: 92%

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells

Crean

Cummins

Bahar

et al. 2015

The Journal of Immunology

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Adenosine receptor–mediated regulation of monocyte/macrophage inflammatory responses is critical in the maintenance of tissue homeostasis. In this study, we reveal that adenosine potently modulates the expression of NR4A1, 2, and 3 orphan nuclear receptors in myeloid cells, and this modulation is primarily through the adenosine A2a receptor subtype. We demonstrate that A2a receptor activation of NR4A1-3 receptor synthesis is further enhanced in TLR4-stimulated monocytes. After TLR4 stimulation, NR4A receptor–depleted monocyte/macrophage cells display significantly altered expression of cell-surface markers and produce increased inflammatory cytokine and chemokine secretion rendering the cells an enhanced proinflammatory phenotype. Exposure of TLR4 or TNF-α–stimulated monocytes to adenosine analogs directs changes in the expression of MIP-3α and IL-23p19, with NR4A2 depletion leading to significantly enhanced expression of these factors. Furthermore, we establish that nuclear levels of NF-κB/p65 are increased in TLR/adenosine-stimulated NR4A2-depleted cells. We show that, after TLR/adenosine receptor stimulation, NR4A2 depletion promotes significant binding of NF-κB/p65 to a κB consensus binding motif within the MIP-3α proximal promoter leading to increased protein secretion, confirming a pivotal role for NF-κB activity in controlling cellular responses and gene expression outcomes in response to these mediators. Thus, these data demonstrate that during an inflammatory response, adenosine modulation of NR4A receptor activity acts to limit NF-κB–mediated effects and that loss of NR4A2 expression leads to enhanced NF-κB activity and hyperinflammatory responses in myeloid cells.

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Section: Nr4a2 and Nr4a3 Regulate Macrophage Inflammatory Gene Expressupporting

confidence: 92%

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells

Crean

Cummins

Bahar

et al. 2015

The Journal of Immunology

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“…A number of investigators have highlighted the importance of these cells in regulating immune-neuroendocrine interactions and adenosine has previously been shown to increase IL-6 release from primary anterior pituitary cell cultures (Ritchie et al 1997). Our recent studies have examined this relationship in more detail.…”

Section: Effects Of Adenosine On Interleukin (Il)-6 Secretion In the mentioning

confidence: 98%

Adenosine signalling pathways in the pituitary gland: one ligand, multiple receptors

Rees

Scanlon²,

Ham³

2003

Journal of Endocrinology

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Adenosine receptors are widely distributed in most species and mediate a diverse range of physiological and pathological effects. Although adenosine receptors have been identified in the pituitary gland, the distribution of the individual subtypes (A 1 , A 2A , A 2B , A 3 ) has not been well defined. Furthermore, the effects of adenosine on pituitary trophic activity and function are not well established despite good evidence for growth-and immunemodulating properties of the nucleoside elsewhere.Recent advances have provided a more detailed description of adenosine receptor distribution and function in the anterior pituitary and this commentary reviews these observations and highlights some of the possible implications in relation to the control of the hypothalamicpituitary-adrenal axis and the regulation of inflammation and pituitary cell growth.

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“…A 2B receptors mediate adenosine inhibition of taurine efflux from pituicytes [417]. It has been claimed that adenosine increases interleukin (IL) 6 and decreases release of tumour necrosis factor from anterior pituitary cells [445]. Adenosine signalling pathways in the pituitary gland have been reviewed, highlighting the effects of adenosine on pituitary cell proliferation and the evidence for opposing actions on endocrine and FSC [438][439][440].…”

Section: Pituitary Gland (Hypophysis)mentioning

confidence: 99%

“…Adenosine increased release of IL-6 from primary anterior pituitary cell cultures [445] and the implications of this finding for inflammation and tumorigenesis were discussed [439]. Adenosine-induced IL-6 expression in FSC is mediated via A 2B receptors coupled to protein kinase (PK) C and p38 mitogen-activated protein kinase (MAPK) [440].…”

Section: Pituitary Gland (Hypophysis)mentioning

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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Adenosine Increases Interleukin 6 Release and Decreases Tumour Necrosis Factor Release From Rat Adrenal Zona Glomerulosa Cells, Ovarian Cells, Anterior Pituitary Cells and Peritoneal Macrophages

Cited by 54 publications

References 0 publications

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells

Adenosine signalling pathways in the pituitary gland: one ligand, multiple receptors

Purinergic signalling in endocrine organs

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