Necrotic cell debris induces a NF-κB-driven inflammasome response in vascular smooth muscle cells derived from abdominal aortic aneurysms (AAA-SMC)

• Verfasst von: Wortmann, Markus [VerfasserIn]
• Verfasst von: Peters, Andreas [VerfasserIn]
• Verfasst von: Hakimi, Maani [VerfasserIn]
• Verfasst von: Böckler, Dittmar [VerfasserIn]
• Verfasst von: Dihlmann, Susanne [VerfasserIn]
• Titel: Necrotic cell debris induces a NF-κB-driven inflammasome response in vascular smooth muscle cells derived from abdominal aortic aneurysms (AAA-SMC)
• Verf.angabe: Markus Wortmann, Ekaterina Skorubskaya, Andreas S. Peters, Maani Hakimi, Dittmar Böckler, Susanne Dihlmann
• E-Jahr: 2019
• Jahr: 16 February 2019
• Umfang: 7 S.
• Fussnoten: Gesehen am 29.03.2019
• Titel Quelle: Enthalten in: Biochemical and biophysical research communications
• Ort Quelle: Orlando, Fla. : Academic Press, 1959
• Jahr Quelle: 2019
• Band/Heft Quelle: 511(2019), 2, Seite 343-349
• ISSN Quelle: 1090-2104
• DOI: doi:10.1016/j.bbrc.2019.02.051
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Abdominal aortic aneurysm
• Sach-SW: AIM2
• Sach-SW: Inflammasome
• Sach-SW: Necrosis
• Sach-SW: NLRP3
• Sach-SW: VSMC
• K10plus-PPN: 1662537182

Abstract

Abdominal aortic aneurysm (AAA) is a multi-factorial progressive vascular disease with life-threatening complications. Increasing evidence suggests that smooth muscle cell (SMC) dysfunction and cell death contribute to dilatation and rupture of the aorta by inducing an inflammatory response. The exact mechanism of this response however, is incompletely understood. We here investigated in vitro the capacity of autologous necrotic cell debris (CD) to induce inflammasome components and inflammatory mediators in aortic SMC (AAA-SMC) isolated from patients with AAA undergoing surgical repair. AAA-SMCs were additionally primed with Interferon- γ (IFN-γ) before treatment with CD in order to mimic the proinflammatory status caused by higher IFN-γ concentrations that have been demonstrated in the wall of AAAs. Real-time RT-PCR revealed that CD significantly increased NLRP3 and IL1B mRNA expression in different SMC cultures within 6h of exposure. Priming of the AAA-SMC with IFN-γ significantly increased expression of NLRP3, AIM2, IFI16 and CASP1 mRNAs, whereas IL1B mRNA was reduced. Additional exposure of IFN-γ-primed AAA-SMC to CD for 6-24h, further augmented expression of AIM2, NLRP3, and Caspase-1 protein levels. Analysis of the SMC supernatants by ELISA revealed CD-induced release of the senescence-associated cytokines IL-6 and MCP-1 in native and IFN-γ-primed SMC, whereas no secretion of Interleukin-(IL) 1α and IL-1β secretion were observed. Our results implicate a role of necrotic cell debris derived from dead neighboring cells in SMC dysfunction and in inflammatory response of AAA tissue.