Search results for "Cyclic adenosine monophosphate"

2013

Graft-versus-host disease (GvHD) is a key contributor to the morbidity and mortality after allogeneic hematopoetic stem cell transplantation (HSCT). Regulatory Foxp3(+) CD4(+) T cells (Treg) suppress conventional T cell activation and can control GvHD. In our previous work, we demonstrate that a basic mechanism of Treg mediated suppression occurs by the transfer of cyclic adenosine monophosphate (cAMP) to responder cells. Whether this mechanism is relevant for Treg mediated suppression of GvHD is currently unknown. To address this question, bone marrow and T cells from C57BL/6 mice were transferred into lethally irradiated BALB/c recipients, and the course of GvHD and survival were monitore…

The human near-term myometrialβ3-adrenoceptor but not theβ2-adrenoceptor is resistant to desensitisation after sustained agonist stimulation

2004

1. In order to compare the beta(2)- and beta(3)-adrenoceptor (beta-AR) desensitisation process in human near-term myometrium, we examined the influence of a pretreatment of myometrial strips with either a beta(2)- or a beta(3)-AR agonist (salbutamol or SR 59119A, respectively, both at 10 microm, for 5 and 15 h) on the relaxation and the cyclic adenosine monophosphate (cAMP) production induced by these agonists. 2. To assess some of the mechanisms potentially implicated in the beta-AR desensitisation process, we studied the influence of such treatment on the number of beta(2)- and beta(3)-AR binding sites, the beta(2)- and beta(3)-AR transcripts expression and the phosphodiesterase 4 (PDE4) …

Perfil farmacológico del roflumilast

2010

Roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-n-(3,5-dichloropyrid-4-yl)benzamide) was the first agent of a novel pharmacological class, selective phosphodiesterase 4 (PDE(4)) inhibitors, approved for the use of chronic obstructive pulmonary disease (COPD). The molecular mechanism of action of roflumilast is inhibition of the PDE(4) isoenzyme with a consequent increase of cyclic adenosine monophosphate. Roflumilast evidently has several pharmacological effects: antiinflammatory, anti-emphysema, and antibiotic actions. This drug also inhibits pulmonary hypertension and reduces mucus hypersecretion. The pharmacological actions leading to these effects are: a) inhibition of reactive oxyg…

REGULATORY ELEMENTS OF THE LEUKAEMIA INHIBITORY FACTOR (LIF) PROMOTER IN MURINE BONE MARROW STROMAL CELLS

1999

Leukaemia inhibitory factor (LIF) plays an important role as a haematopoietically active cytokine. As described earlier in a murine model, interleukin 1 (IL-1) induced LIF mRNA and protein expression. We utilized the murine cell line +/+-1.LDA11 to further define regulatory mechanisms of LIF expression in bone marrow stromal cells. The production of LIF mRNA is stimulated by IL-1beta, TNF-alpha, and the cAMP analogue 8-bromoadenosine 3':5'-monophosphate (8BrcAMP). LIF mRNA expression is controlled at the transcriptional level. Different fragments from -542 to -45 bp 5' upstream of the transcriptional start site of the murine LIF gene were fused to the luciferase gene. All LIF-promoter lucif…

CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.

2008

T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcεRI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells and MCs, respectively. When activated in the presence of Treg cells, MCs showed increased cyclic adenosine monophosphate (cAMP) concentrations and reduced Ca2+ influx, independently of phospholipase C (PLC)-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effec…

Circadian rhythm and effects of light on cAMP content of the dwarf hamster suprachiasmatic nucleus

1998

The present study was conducted in the dwarf hamster (Phodopus sungorus) to investigate whether a circadian rhythm is present in the content of the second messenger cyclic adenosine 3',5'-monophosphate (cAMP) in the suprachiasmatic nucleus (SCN), the endogenous clock in mammals. In animals held under light/dark conditions (LD), we observed high levels at the end of the light phase and low levels during the night in frozen SCN punches. In animals held in continuous dark, a similar rhythm was seen although a second peak was present in the subjective day. In senile hamsters under LD, the decrease of cAMP levels at the light transition was not seen. These data, obtained for the first time from …

Clinical Relevance of Thyroid-Stimulating Immunoglobulins in Graves' Ophthalmopathy

2011

Purpose Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO. Design Cross-sectional trial. Participants A total of 108 untreated patients with GO. Methods Thyroid-stimulating immunoglobulins, assessed with a novel bioassay, bind to the thyrotropin receptor (TSHR) and transmit signals for cyclic adenosine monophosphate (cAMP)-dependent activation of luciferase gene expression. The cAMP/cAMP response element-binding protein/cAMP-regulatory element complex induces luciferase that is quantified after cell lysis. The TSI levels were correlated with activity and severity of GO and compa…

Intestinal filtration as a consequence of increased mucosal hydraulic permeability

1980

Two mechanisms have been proposed to explain the secretory action of laxative compounds in the intestine: 1. increase of the intracellular amount of cyclic adenosine monophosphate due to stimulation of the adenylate cyclase system and 2. inhibition of intestinal transfer processes, in particular the Na,K-ATPase activated sodium absorption. In a set of in vivo and in vitro experiments in rat colon it could be demonstrated that dihydroxy bile acids (deoxycholate) and diphenolic laxatives (oxyphenisatin) enhance the hydraulic permeability of the mucosal tissue. The permeability changes take place--and there is good experimental evidence--at the zonulae occludentes which bind the epithelial cel…

The phototransduction cascade in the isolated chick pineal gland revisited.

2003

It is well established that the isolated chick pineal gland is directly light sensitive and that melatonin synthesis of the gland can be inhibited by exposing the gland to light during scotophase. Since not all the steps of the phototransduction cascade have been clarified to the same extent as in the retina, we have treated isolated chick pineal glands with 90 min of light during scotophase and with drugs that affect key-components of vertebrate phototransduction, i.e., cyclic guanosine monophosphate (cGMP) phosphodiesterase 6 (PDE6), cGMP levels and cGMP-gated calcium channels. The endpoint measured was the activity of the rate-limiting enzyme of melatonin synthesis, arylalkylamine N-acet…

Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells

2011

Abstract The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP repression, however,…