Adrenergic stimulation alters the expression of inflammasome components and interleukins in primary human monocytes

Abstract

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 the ex vivo protein 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.

Expression of Toll-Like Receptors in the Animal Model of Bladder Outlet Obstruction

“…IL-18 is excreted in a constitutive manner so an alpha-1 adrenergic receptor antagonist would seem to interfere with its production [ 46 ]. This is consistent with the study by Horstmann et al in which human monocytes stimulated by phenylephrine (alpha-1 receptor agonist) resulted in the upregulation of IL-18 [ 47 ].…”

The NLRP3 p.A441V Mutation in NLRP3‐AID Pathogenesis: Functional Consequences, Phenotype‐Genotype Correlations and Evidence for a Recurrent Mutational Event

“…Expression levels of NLRP3 transcripts at basal conditions (M0) were similar in Proband I; the same six available patients out of crisis from Family I, Proband II; and the healthy controls (Ct~31, mean Ct~31, Ct~29, and mean Ct~31.7, respectively). In accordance with previous studies , LPS induced NLRP3 expression in monocytes from healthy donors. A similar increase was observed in the two probands and in patients out of crisis from Family I (Figure ).…”

Caspase‐1 inflammasome activity in patients with Staphylococcus aureus bacteremia

“…Such an immunosuppressed state could explain the more complicated disease course of these patients. A suppressed immune response involving downregulated mRNA expression of NLRP1 accompanied by normal levels of IL1B and CASP1 mRNAs has been observed in ex vivo stimulated monocytes in patients with trauma, and reduced NLRP3 gene expression in patients suffering polytrauma has also been discussed . In addition, the patients with complicated SAB in the present study displayed downregulated mRNA levels of the immunosuppression marker human leucocyte antigen‐DRA, HLA‐DRA , recently shown by our group, indicating an immunocompromised state …”