The Role of β2-Adrenergic Receptors in Inflammation and Allergy

Abstract

Essential role of beta(2)-adrenoreceptor (beta(2)AR) in airway relaxation is well established. Nevertheless, beta(2)AR seems playing an actual role in allergy and inflammation. Interaction between beta(2)AR and proinflamatory cytokines in airway smooth muscle has been revealed. Being located on proinflamatory cells, beta(2)ARs may influence function of these cells in vivo. It was clear established, that stimulation of beta(2)AR inhibits release of proinflamatory mediators from mast cells, influences T-cell growth and function, eosinophil survival and function, including GM-CSF- or PAF-induced degranulation. Stimulation of beta(2)ARs, located on alveolar macrophages and epithelial cells, has ambiguity influence on their regulation and function, including phagocytosis and mediator secretion, in vivo. Vascular responses, resulting in inhibition of plasma exudation were confirmed, but modulation of sensory nerves via beta(2)AR is not certain yet. beta(2)AR-agonists are effective in treatment of immediate allergic reactions, but desensitisation of beta(2)ARs on inflammatory cells may result in paradoxical effects, especially in asthma. In summary, it is clear that beta(2)ARs may play an anti-inflammatory role in vitro. Unfortunately, in vitro data have shown limited applicability in vivo; therefore further research in this field is required.

Compounds That Increase or Mimic Cyclic Adenosine Monophosphate Enhance Tristetraprolin Degradation in Lipopolysaccharide-Treated Murine J774 Macrophages

“…The results described here provide a mechanism by which the expression of TTP can be turned off at sites of inflammation. ␤ 2 -Agonists have been reported to have antiinflammatory effects in various in vitro conditions but these actions do not clearly translate into the in vivo situation, e.g., in inflamed lung tissue in patients with asthma (Sitkauskiene and Sakalauskas, 2005). The mechanism described in the present study and in our earlier study (Jalonen et al, 2007) could, at least partly, explain the discrepancy between these in vitro and in vivo findings.…”

Salbutamol increases tristetraprolin expression in macrophages

“…In addition to bronchodilatation, salbutamol and other β 2 -agonists have been shown to have some anti-inflammatory effects (Bissonnette and Befus, 1997;Broadley, 2006;Johnson, 2002;Sitkauskiene and Sakalauskas, 2005). Inflammatory cells including macrophages express β 2 -adrenoceptors on their cell surface.…”

“…Activation of β 2 -adrenoceptors leads to a series of events that induce airway smooth muscle relaxation and also to some antiinflammatory effects (Bissonnette and Befus, 1997;Broadley, 2006;Giembycz and Newton, 2006;Johnson, 2002Johnson, , 2006Sitkauskiene and Sakalauskas, 2005). β 2 -adrenoceptors activate adenylate cyclase that results in increased intracellular cAMP levels and activation of protein kinase A (PKA), which in turn regulates phosphorylation (activation) of target molecules and gene expression.…”

“…β 2 -adrenoceptors activate adenylate cyclase that results in increased intracellular cAMP levels and activation of protein kinase A (PKA), which in turn regulates phosphorylation (activation) of target molecules and gene expression. Table 1 Primer and probe sequences Primer Sequence mTTP forward 5′-CTCAGAAAGCGGGCGTTGT-3′ mTTP reverse 5′-GATTGGCTTGGCGAAGTTCA-3′ mTTP probe 5′-Fam-CCAAGTGCCAGTTTGCTCACGGC-Tamra-3′ mGAPDH forward 5′-GCATGGCCTTCCGTGTTC-3′ mGAPDH reverse 5′-GATGTCATCATACTTGGCAGGTTT-3′ mGAPDH probe 5′-Fam-TCGTGGATCTGACGTGCCGCC-Tamra-3′ hTTP forward 5′-CCCCAAATACAAGACGGAACTC-3′ hTTP reverse 5′-GGGCCGCCAGGTCTTC-3′ hTTP probe 5′-Fam-CCCTACGGCTCTCGCTGCCACTT-Tamra-3′ hGAPDH forward 5′-AAGGTCGGAGTCAACGGATTT-3′ hGAPDH reverse 5′-GCAACAATATCCACTTTACCAGAGTTAA-3′ hGAPDH probe 5′-Fam-CGCCTGGTCACCAGGGCTGC-Tamra-3′ β 2 -agonists have been shown to inhibit TNF-α and GM-CSF release from human mast cells, blood monocytes, macrophages, lyphocytes, and epithelial cells, and demonstrate their anti-inflammatory effects possibly through elevation of cAMP levels (Bissonnette and Befus, 1997;Broadley, 2006;Izeboud et al, 1999;Johnson, 2002;Sitkauskiene and Sakalauskas, 2005). There is tentative data that an activator of adenylate cyclase, forskolin, and an analog of cAMP, dibutyryl-cAMP, may increase TTP mRNA levels (DuBois et al, 1990;Kaneda et al, 1992).…”

What the Genetic Background of Individuals with Asthma and Obesity Can Reveal: Is β2-Adrenergic Receptor Gene Polymorphism Important?

“…ADRB2 stimulation could induce IgE production by human B lymphocytes and expression of the soluble low-affinity IgE receptor sCD23. 36,37 Obesity and ADRB2 Polymorphisms While it has been estimated that genetics explains 40% of population variability in the prevalence of obesity, conflicting results exist for the association of the ADRB2 Arg16 polymorphism and obesity. Several studies reported that increased BMI was associated with the Arg16 isoform, while other studies have revealed the opposite results.…”