Modulation of glucocorticoid receptor activity by cyclic nucleotides and its implications on the regulation of human skin fibroblast growth and protein synthesis

Oikarinen, Jouko; Hämäläinen, Leena; Oikarinen, Aarne

doi:10.1016/0304-4165(84)90290-3

Cited by 62 publications

(19 citation statements)

References 30 publications

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“…Such an effect would be consistent with the enhanced GR:DNA binding seen in cells overexpressing PKA (56). Another possibility is that cAMPelevating agents increase the expression of functional GR (57) and/or stabilize the interaction of glucocorticoid-bound GR with DNA through activation of PKA (58). Although these are FIGURE 11.…”

Section: Mechanism Of Actionmentioning

confidence: 60%

Selective Prostacyclin Receptor Agonism Augments Glucocorticoid-Induced Gene Expression in Human Bronchial Epithelial Cells

Wilson

Shen²,

Rider³

et al. 2009

The Journal of Immunology

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Prostacyclin receptor (IP-receptor) agonists display anti-inflammatory and antiviral activity in cell-based assays and in preclinical models of asthma and chronic obstructive pulmonary disease. In this study, we have extended these observations by demonstrating that IP-receptor activation also can enhance the ability of glucocorticoids to induce genes with anti-inflammatory activity. BEAS-2B bronchial epithelial cells stably transfected with a glucocorticoid response element (GRE) luciferase reporter were activated in a concentration-dependent manner by the glucocorticoid dexamethasone. An IP-receptor agonist, taprostene, increased cAMP in these cells and augmented luciferase expression at all concentrations of dexamethasone examined. Analysis of the concentration-response relationship that described this effect showed that taprostene increased the magnitude of transcription without affecting the potency of dexamethasone and was, thus, steroid-sparing in this simple system. RO3244794, an IP-receptor antagonist, and oligonucleotides that selectively silenced the IP-receptor gene, PTGIR, abolished these effects of taprostene. Infection of BEAS-2B GRE reporter cells with an adenovirus vector encoding a highly selective inhibitor of cAMP-dependent protein kinase (PKA) also prevented taprostene from enhancing GRE-dependent transcription. In BEAS-2B cells and primary cultures of human airway epithelial cells, taprostene and dexamethasone interacted either additively or cooperatively in the expression of three glucocorticoid-inducible genes (GILZ, MKP-1, and p57kip2) that have anti-inflammatory potential. Collectively, these data show that IP-receptor agonists can augment the ability of glucocorticoids to induce anti-inflammatory genes in human airway epithelial cells by activating a cAMP/PKA-dependent mechanism. This observation may have clinical relevance in the treatment of airway inflammatory diseases that are either refractory or respond suboptimally to glucocorticoids.

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Section: Mechanism Of Actionmentioning

confidence: 60%

Selective Prostacyclin Receptor Agonism Augments Glucocorticoid-Induced Gene Expression in Human Bronchial Epithelial Cells

Wilson

Shen²,

Rider³

et al. 2009

The Journal of Immunology

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“…However, it is also possible that an increase in translocation of the GR to the nuclei, caused by the increases in corticosterone serum levels and/or altered inputs to the cell groups, is responsible for the selective increases in GR IR observed. As a matter of fact, cyclic nucleotides have been implicated to regulate both glucocorticoid (Oikarinen et al, 1984;Gruol et al, 1986) and estrogen (Fleming et at., 1982) receptors and it cannot be excluded that activation of the stress sensitive A 6 and B 7 second messenger systems might cause an increased ligand binding leading to increased translocation of the GR in these areas.…”

Section: Discussionmentioning

confidence: 97%

Chronic immobilization stress: evidence for decreases of 5-hydroxy-tryptamine immunoreactivity and for increases of glucocorticoid receptor immunoreactivity in various brain regions of the male rat

Kitayama

Cintra

Janson

et al. 1989

J. Neural Transmission

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Male rats were exposed to severe 14 day immobilization stress. Body weight, body temperature, food and water intake, behavioral parameters, and serum corticosterone levels were measured during and after the stress period. On the 7th day after cessation of stress the experimental animals together with the control rats were taken to immunocytochemical analysis involving morphometry and microdensitometry of tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), various neuropeptide, and glucocorticoid receptor (GR) immunoreactivities (IRs) in a large number of regions of the central nervous system. In addition, adrenocorticotropic hormone (ACTH) IR was analyzed in the pituitary gland. Seven days following cessation of the chronic stress food intake, total locomotion and forward locomotion had been restored to normal. Serum corticosterone levels appeared to remain increased even 6 days following cessation of the chronic immobilization stress, probably caused by increased release of ACTH. Paraventricular corticotropin releasing hormone (CRF) IR was negatively correlated with the pituitary ACTH IR, indicating that the increase in ACTH release was produced by an increased release of CRF from the hypothalamus. The major immunocytochemical change observed 7 days after cessation of stress was a disappearance of 5-HT IR in the 5-HT cell groups B1, B2, B3, and B7. 5-HT IR in nerve terminals was only affected in the dorsal horn, where 5-HT IR was increased in the substantia gelatinosa. GR IR was found to be significantly increased in monoaminergic cell groups: serotoninergic B7, dopaminergic A12, and noradrenergic A1, A2, and A6. A trend for a reduction of TH IR was observed in nigral DA cells associated with significant reductions in TH IR in striatal DA nerve terminals. Finally, increases in 5-HT and substance P (SP) IR were found in the nerve terminals of the substantia gelatinosa of the cervical spinal cord in the stress group. In the present experimental model evidence has been obtained for a maintained activation of the hypothalamic-pituitary-adrenal axis as evaluated 7 days after cessation of severe chronic immobilization stress. The reduction of 5-HT IR in various 5-HT cell groups indicates a reduction of 5-HT synthesis, which may also be associated with reduced 5-HT release from the nerve terminals, since no depletion was observed in terminal regions and in one case an increase in 5-HT IR was noted (substantia gelatinosa).(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Previous studies using cGMP have yielded conflicting results. cGMP decreases the number of steroid-bound GR in human fibroblasts by approximately one-third but has no effect on GR steroid binding in a mouse thymoma cell line (35,36). In rat uterine cells, cGMP has no effect on PR steroid binding or protein (37).…”

Section: Discussionmentioning

confidence: 99%

Atrial natriuretic peptide inhibits mineralocorticoid receptor function in rat colonic surface cells.

Schulman¹,

Lindemeyer²,

Barman³

et al. 1996

J. Clin. Invest.

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Modulation of glucocorticoid receptor activity by cyclic nucleotides and its implications on the regulation of human skin fibroblast growth and protein synthesis

Cited by 62 publications

References 30 publications

Selective Prostacyclin Receptor Agonism Augments Glucocorticoid-Induced Gene Expression in Human Bronchial Epithelial Cells

Selective Prostacyclin Receptor Agonism Augments Glucocorticoid-Induced Gene Expression in Human Bronchial Epithelial Cells

Chronic immobilization stress: evidence for decreases of 5-hydroxy-tryptamine immunoreactivity and for increases of glucocorticoid receptor immunoreactivity in various brain regions of the male rat

Atrial natriuretic peptide inhibits mineralocorticoid receptor function in rat colonic surface cells.

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