Multiple G-protein-coupling specificity of beta-adrenoceptor in macrophages.

Adrenergic signalling of the immune system is one of the important modulator pathways of the inflammatory immune response realized via G protein-mediated pathways. The resulted signal depends on the type of the receptor-coupled G-protein (GPCR) that, according to the classical paradigm in the case of beta-adrenergic receptor (beta-AR), is Gs-type. Recently, alternate and/or multiple G protein coupling specificity of GPCRs have been demonstrated including a switch from Gs to Gi binding.

The catecholamine cytokine balance: interaction between the brain and the immune system.

Cytokines are involved both in various immune reactions and in controlling certain events in the central nervous system (CNS). In our earlier studies, it was shown that monoamine neurotransmitters, released in stress situations, represent a tonic sympathetic control on cytokine production and on the balance of proinflammatory/anti-inflammatory cytokines. Basic and clinical studies have provided evidence that the biophase level of monoamines, determined by the balance of their release and uptake, is involved in the pathophysiology and treatment of depression, while inflammatory mediators might also have a role in its etiology.

Dual beta-adrenergic modulation in the immune system: stimulus-dependent effect of isoproterenol on MAPK activation and inflammatory mediator production in macrophages.

This is the first study to demonstrate that the interaction between beta-adrenoceptor activation, and the production of inflammatory mediators can be modulated in opposite ways by two inflammatory stimuli, namely, protein kinase C (PKC)-activating phorbol myristyl acetate (PMA) and lipopolysaccharide (LPS). We provided evidence that isoproterenol treatment, when combined with phorbol ester increased the production of tumor necrosis factor-alpha, interleukin-12, and nitric oxide in murine macrophages, as well as in human monocytes and differentiated PLB-985 cells, while in agreement with earlier findings, it decreased inflammatory mediator production in combination with LPS stimulation. The contrasting effect on inflammatory mediator production, shown for the PMA and LPS activated cells was accompanied by parallel changes in activation of ERK1/2 and p38 MAPKs.

Endotoxin-induced TNF-alpha production changes inversely to its plasma level during pregnancy.

Objective: To study plasma TNF-alpha levels during normal pregnancy and the ex vivo endotoxin-induced TNF-alpha production of peripheral blood cells.

Study Design: In a longitudinal prospective study the ex vivo endotoxin-induced TNF-alpha production of peripheral blood cells and the plasma level of TNF-alpha in 18 women with uncomplicated pregnancies were determined at the 8th, 17th, 27th and 36th weeks of their pregnancy and 48 h and 6 weeks post-delivery. TNF-alpha levels were determined by ELISA technique.

The inducibility of TNF-alpha production is different in the granulocytic and monocytic differentiated forms of wild type and CGD-mutant PLB-985 cells.

Chronic granulomatous disease is an inherited disorder associated with a defect in phagocytic cell oxidative metabolism resulting in ineffective microbicidal activity. Consequently, patients with chronic granulomatous disease suffer from recurrent infections. Published data show that besides the failure to produce superoxide and its derivatives, other functional problems can also be found in chronic granulomatous disease-mutant cells.