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

• Published in: Biochemical and biophysical research communications Vol. 511; no. 2; pp. 343 - 349
• Main Authors: Wortmann, Markus, Skorubskaya, Ekaterina, Peters, Andreas S., Hakimi, Maani, Böckler, Dittmar, Dihlmann, Susanne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.04.2019
• Subjects: Abdominal aortic aneurysm; AIM2; Aorta, Abdominal - cytology; Aorta, Abdominal - immunology; Aorta, Abdominal - pathology; Aortic Aneurysm, Abdominal - complications; Aortic Aneurysm, Abdominal - immunology; Aortic Aneurysm, Abdominal - pathology; Cells, Cultured; Humans; Inflammasome; Inflammasomes - immunology; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - immunology; Myocytes, Smooth Muscle - pathology; Necrosis; Necrosis - complications; Necrosis - immunology; Necrosis - pathology; NF-kappa B - immunology; NLRP3; VSMC; NLRP3; Inflammasome; AIM2; VSMC; Abdominal aortic aneurysm; Necrosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.02.051

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 6 h 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 6–24 h, 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. [Display omitted] •Autologous necrotic cell debris induces NLRP3 and IL1B gene expression in SMC derived from abdominal aortic aneurysms (AAA).•Autologous necrotic cell debris increases protein expression of AIM2, NLRP3, and Caspase-1 in Interferon-γ-primed AAA-SMC.•Autologous necrotic cell debris induces release of MCP-1 and IL-6 from AAA-SMC.•Induction is mediated by NF-kB signaling, i.e. by increased phosphorylation of the p65 subunit of NF-kB.•The data implicate a role of dead neighboring cells in SMC dysfunction and in inflammatory response of AAA tissue.