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

Horstmann,Johann‑Philipp; Marzi,Ingo; Relja,Borna

doi:10.3892/etm.2015.2850

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

Authors:
- Johann‑Philipp Horstmann
- Ingo Marzi
- Borna Relja
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Affiliations: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe‑University, Frankfurt 60590, Germany
Published online on: November 10, 2015 https://doi.org/10.3892/etm.2015.2850
Pages: 297-302

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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.

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