Pro-inflammatory responses in human monocytes are beta1-adrenergic receptor subtype dependent.

Molecular Immunology
Laurel A GrisantiJames E Porter

Abstract

Stress induced circulating catecholamines are hypothesized to selectively activate adrenergic receptors (ARs) on immunocompetent cells modulating their inflammatory response to trauma or environmental toxins. We characterized changes in expression of a pro-inflammatory cytokine modulated by beta-AR activation in human primary and immortalized monocytes that had been simultaneously stimulated with lipopolysaccharide (LPS). Results from cytokine antibody arrays demonstrated that half-maximal effective concentrations of the selective beta-AR agonist isoproterenol (Iso) qualitatively increased LPS-mediated expression of the soluble cytokine, interleukin-1beta (IL-1beta). Semi-quantitative immunoblot techniques confirmed a synergistic increase of IL-1beta production in both LPS stimulated THP-1 cells and primary human monocytes co-incubated with Iso. Immunoblot techniques as well as radioligand binding studies were also used to characterize the heterogeneous expression of beta(1)- and beta(2)-AR subtypes on THP-1 cells. beta-AR activation is classically associated with generation of cAMP in many tissues and cell types. Therefore, using the method of Schild, we generated Iso concentration-response curves in the presence of fixed subt...Continue Reading

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