title: Adrenergic stimulation alters the expression of inflammasome components and interleukins in primary human monocytes.
abstract: Prior to their release, interleukin (IL)-1β and IL-18 are cleaved to their bioactive forms by a multiprotein complex known as an inflammasome, which is comprised of a number of elements that are subject to nuclear factor-κB-dependent transcription. Catecholamines have been indicated to exert an enhancing effect on the IL-1β release. The aim of the present study was to determine whether alterations in inflammasome gene expression may be responsible for the modified IL-1β and IL-18 secretion following lipopolysaccharide (LPS) and catecholamine co-stimulation. Monocytes were isolated from the peripheral blood of 21 healthy volunteers using CD14+microbeads. Following stimulation with LPS (2 µg/ml) and/or phenylephrine (PE; 10 µM) for 24 h, the supernatants were subjected to ELISA to evaluate theex vivoprotein expression levels of IL-1β and IL-18. In addition, the gene expression levels of inflammasome components associated with the cleavage of IL-1β and IL-18, including NLRP1, NLRP3, caspase-1 and PYCARD were determined using polymerase chain reaction. The results indicated that LPS significantly increased IL-1β expression compared with the unstimulated control samples. Co-stimulation with LPS + PE significantly enhanced IL-1β expression compared with LPS alone. Furthermore, IL-18 expression was significantly reduced by LPS and LPS + PE co-stimulation. The gene expression levels of IL-18, NLRP1, caspase-1 and PYCARD were comparable in the LPS- and LPS + PE-stimulated cells. LPS significantly induced the expression levels of IL-1β and NLRP3, and to a lesser degree, the expression of NLRP1, compared with the control. By contrast, PE markedly induced the expression levels of IL-18 and NLRP1, while LPS reduced the gene expression of IL-18. In conclusion, adrenergic stimulation suppressed NLRP3 expression and enhanced NLRP1 expression, indicating that NLRP3 may regulate IL-1β secretion and NLRP1 may regulate the release of IL-18.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt 60590, Germany.
authors.forename: Johann-Philipp
authors.initials: JP
authors.lastname: Horstmann
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt 60590, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Marzi
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt 60590, Germany.
authors.forename: Borna
authors.initials: B
authors.lastname: Relja
keywords: LRR and PYD domains-containing protein; NACHT; adrenergic effects; catecholamines; inflammasome; interleukin-1β; monocytes