Multiple cAMP-induced signaling cascades regulate prolactin expression in T cells

Abstract

Abstract. Beside its pivotal role in reproduction, the pituitary hormone prolactin (PRL) has been attributed an immunomodulatory function. Here we report that cAMP is an important stimulator of PRL transcription in primary human T lymphocytes. Inhibition of both protein kinase A (PKA) and p38 MAPK partially abrogated cAMPinduced PRL expression. In addition, cAMP-induced phosphorylation of p38 was shown to occur independently of PKA and could be mimicked by a methylated Cell. Mol. Life Sci. 63 (2006) 0092-0099 1420-682X/06/010092-8420-682X/05/15-1-13 DOI 10.1007/s00018-005-5433-4 © Birkhäuser Verlag, Basel, 2006 cAMP analogue which specifically activates the recently discovered cAMP receptor EPAC (exchange protein directly activated by cAMP). Our findings suggest that cAMP induces PRL expression in T lymphocytes via cooperation of at least two different signaling pathways: a PKA-dependent pathway leading to the phosphorylation of cAMP response element-binding protein, and a PKAindependent pathway leading to p38 phosphorylation.

Prolactin down-regulates CD4+CD25hiCD127low/− regulatory T cell function in humans

“…Our results showed that both T eff and T reg cells constitutively expressed PRL mRNA; this is different from PRL receptor expression, which is only constitutively expressed in T reg cells. In addition, we showed that PRL mRNA expression did not increase in T eff or T reg cells when they were activated with anti-CD3/ CD28; these results differed from a previously published report in which the authors observed an increase in PRL mRNA expression in T cells (Gerlo et al 2006). This difference could be accounted for in several ways.…”

Exchange Protein Directly Activated by cAMP (epac): A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions

“…Epac1 is most abundant in the heart, kidney, blood vessels, adipose tissue, central nervous system, ovary, and uterus (de Rooij et al, 1998;Kawasaki et al, 1998), whereas Epac2 splice variants (Epac2A Biology of the Epac Signalosome and Epac2B) are mostly expressed in the central nervous system (Epac2A), adrenal gland (Epac2B), and pancreas (Epac2A; (de Rooij et al, 1998;Kawasaki et al, 1998;Niimura et al, 2009). Additionally, expression of Epac1 has been found to be present in monocytes, macrophages, B and T lymphocytes, eosinophils, neutrophils, platelets, and in CD34-positive hematopoietic cells (Tiwari et al, 2004;Bryn et al, 2006;Gerlo et al, 2006), whereas Epac2 was undetectable in all studied hematopoietic cell types (Tiwari et al, 2004). Neurite outgrowth and axon regeneration require Epac2 upregulation and Epac1 downregulation in adults (Murray and Shewan, 2008;Murray et al, 2009a).…”

cAMP/CREB-mediated Transcriptional Regulation of Ectonucleoside Triphosphate Diphosphohydrolase 1 (CD39) Expression

“…This ecto-apyrase activity modulates many of the purinergic signaling processes in which ATP or ADP play a role, and is important for the tonic maintenance of vascular homeostatic properties related to inflammation, coagulation, vasodilation, and barrier function. For instance, CD39 can inhibit platelet activation and maintain vascular fluidity in the complete absence of prostacyclin and nitric oxide as well as regulate immune function and provide protection from both cardiac and cerebral ischemia and reperfusion injuries (1)(2)(3)(4)(5)(6)(7)(8)(9).…”