Hannah P Priyanka1, Srinivasan ThyagaRajan. 1. Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
Abstract
UNLABELLED: The mechanistic implications of the presence of sympathetic noradrenergic innervation in lymphoid organs in synaptic association with lymphocytes open to the influence of hormonal fluctuations throughout reproductive age in females has not been investigated yet. OBJECTIVES: The aim of the present study is to investigate the role of alpha-adrenoceptors (α-ARs) and estrogen in modulating immune responses in the spleen through intracellular signaling targets such as ERK 1/2, CREB, Akt, NF-κB. METHODS: Splenocytes from young Sprague-Dawley rats were incubated with α1- and α2- AR specific agonists, phenylephrine and clonidine, without and with 17b-estradiol or specific antagonists prazosin and idazoxan to examine their effects on proliferation, cytokine production, nitric oxide production, and intracellular signaling molecules. RESULTS: α1-AR stimulation inhibited lymphocyte proliferation and IFN-g production and enhanced IL-2, p-ERK and p-CREB expression. Co-stimulation using estrogen enhanced cytokine production and suppressed p-Akt expression. α1-AR blockade reversed agonist-induced IL-2 production alone. α2-AR stimulation inhibited lymphocyte proliferation, p-ERK and p-CREB expression, and increased p-NF-kB and p-Akt expression. Co-stimulation with estrogen increased IL-2 and suppressed p-CREB expression. α2-AR Idazoxan prevented IL-2 production in the absence and presence of estrogen, and reversed clonidine-induced increase in NO production and p-ERK and p-Akt expression in the presence of estrogen. CONCLUSIONS: These results suggest that the cell-mediated immune responses are selectively modulated depending upon the subtypes of α-AR and further, these effects are differentially regulated in the presence of estrogen mediated through selective alteration in the intracellular signaling pathways involving ERK, CREB, Akt, and NF-κB.
UNLABELLED: The mechanistic implications of the presence of sympathetic noradrenergic innervation in lymphoid organs in synaptic association with lymphocytes open to the influence of hormonal fluctuations throughout reproductive age in females has not been investigated yet. OBJECTIVES: The aim of the present study is to investigate the role of alpha-adrenoceptors (α-ARs) and estrogen in modulating immune responses in the spleen through intracellular signaling targets such as ERK 1/2, CREB, Akt, NF-κB. METHODS: Splenocytes from young Sprague-Dawley rats were incubated with α1- and α2- AR specific agonists, phenylephrine and clonidine, without and with 17b-estradiol or specific antagonists prazosin and idazoxan to examine their effects on proliferation, cytokine production, nitric oxide production, and intracellular signaling molecules. RESULTS: α1-AR stimulation inhibited lymphocyte proliferation and IFN-g production and enhanced IL-2, p-ERK and p-CREB expression. Co-stimulation using estrogen enhanced cytokine production and suppressed p-Akt expression. α1-AR blockade reversed agonist-induced IL-2 production alone. α2-AR stimulation inhibited lymphocyte proliferation, p-ERK and p-CREB expression, and increased p-NF-kB and p-Akt expression. Co-stimulation with estrogen increased IL-2 and suppressed p-CREB expression. α2-AR Idazoxan prevented IL-2 production in the absence and presence of estrogen, and reversed clonidine-induced increase in NO production and p-ERK and p-Akt expression in the presence of estrogen. CONCLUSIONS: These results suggest that the cell-mediated immune responses are selectively modulated depending upon the subtypes of α-AR and further, these effects are differentially regulated in the presence of estrogen mediated through selective alteration in the intracellular signaling pathways involving ERK, CREB, Akt, and NF-κB.
Authors: Sharon W Way; Joseph R Podojil; Benjamin L Clayton; Anita Zaremba; Tassie L Collins; Rejani B Kunjamma; Andrew P Robinson; Pedro Brugarolas; Robert H Miller; Stephen D Miller; Brian Popko Journal: Nat Commun Date: 2015-03-13 Impact factor: 14.919