β2-Adrenergic receptors in immunity and inflammation: Stressing NF-κB

β2-Adrenergic receptors (β2-ARs) transduce the effects of (nor)epinephrine on a variety of cell types and act as key mediators of the body's reaction to stress. β2-ARs are also expressed on immune cells and there is ample evidence for their role in immunomodulation. A key regulator of the immune response and a target for regulation by stress-induced signals is the transcription factor Nuclear Factor-kappaB (NF-κB). NF-κB shapes the course of both innate and adaptive immune responses and plays an important role in susceptibility to disease. In this review, we summarise the literature that has been accumulated in the past 20years on adrenergic modulation of NF-κB function. We here focus on the molecular basis of the reported interactions and show that both physiological and pharmacological triggers of β2-ARs intersect with the NF-κB signalling cascade at different levels. Importantly, the action of β2-AR-derived signals on NF-κB activity appears to be highly cell type specific and gene selective, providing opportunities for the development of selective NF-κB modulators.

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