Skip to main content
Top
Published in: Immunity & Ageing 1/2015

Open Access 01-12-2015 | Short report

Gene expression of inflammasome components in peripheral blood mononuclear cells (PBMC) of vascular patients increases with age

Authors: Xiaoyu Wu, Maani Hakimi, Markus Wortmann, Jian Zhang, Dittmar Böckler, Susanne Dihlmann

Published in: Immunity & Ageing | Issue 1/2015

Login to get access

Abstract

Background

Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22–82) in association with age.

Findings

Linear regression of real-time qRT-PCR data revealed a significant positive association of gene expression of each of the inflammasome components with age (Pearson correlation coefficients: AIM2: r = 0.245; P = 0.032; NLRP3: r = 0.367; P = 0.001; ASC (PYCARD): r = 0.252; P = 0.027; CASP1: r = 0.296; P = 0.009; CASP5: r = 0.453; P = 0.00003; IL1B: r = 0.247; P = 0.030). No difference in gene expression of AIM2, NLRP3, ASC CASP1, and CASP5 was detected between PBMC of patients with advanced atherosclerosis and other vascular patients, whereas IL1B expression was increased in PBMC of the latter group (P = 0.0005).

Conclusion

The findings reinforce the systemic pro-inflammatory phenotype reported in elderly by demonstrating an increased phase-1 activation of inflammasomes in PBMC of vascular patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.CrossRefPubMed Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.CrossRefPubMed
2.
go back to reference Larbi A, Franceschi C, Mazzatti D, Solana R, Wikby A, Pawelec G. Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda). 2008;23:64–74.CrossRef Larbi A, Franceschi C, Mazzatti D, Solana R, Wikby A, Pawelec G. Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda). 2008;23:64–74.CrossRef
3.
go back to reference Kovacs EJ, Palmer JL, Fortin CF, Fülöp Jr T, Goldstein DR, Linton PJ. Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors. Trends Immunol. 2009;30(7):319–24.PubMedCentralCrossRefPubMed Kovacs EJ, Palmer JL, Fortin CF, Fülöp Jr T, Goldstein DR, Linton PJ. Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors. Trends Immunol. 2009;30(7):319–24.PubMedCentralCrossRefPubMed
4.
go back to reference Pinke KH, Calzavara B, Faria PF, do Nascimento MP, Venturini J, Lara VS. Proinflammatory profile of in vitro monocytes in the ageing is affected by lymphocytes presence. Immun Ageing. 2013;10(1):22.PubMedCentralCrossRefPubMed Pinke KH, Calzavara B, Faria PF, do Nascimento MP, Venturini J, Lara VS. Proinflammatory profile of in vitro monocytes in the ageing is affected by lymphocytes presence. Immun Ageing. 2013;10(1):22.PubMedCentralCrossRefPubMed
5.
go back to reference Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, et al. The origins of age-related proinflammatory state. Blood. 2005;105(6):2294–9.CrossRefPubMed Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, et al. The origins of age-related proinflammatory state. Blood. 2005;105(6):2294–9.CrossRefPubMed
6.
go back to reference Dinarello CA. Interleukin-1beta and the autoinflammatory diseases. N Engl J Med. 2009;360(23):2467–70.CrossRefPubMed Dinarello CA. Interleukin-1beta and the autoinflammatory diseases. N Engl J Med. 2009;360(23):2467–70.CrossRefPubMed
8.
go back to reference Goldberg R, Prescott N, Lord GM, MacDonald TT, Powell N. The unusual suspects-innate lymphoid cells as novel therapeutic targets in IBD. Nat Rev Gastroenterol Hepatol. 2015;12(5):271–83.CrossRefPubMed Goldberg R, Prescott N, Lord GM, MacDonald TT, Powell N. The unusual suspects-innate lymphoid cells as novel therapeutic targets in IBD. Nat Rev Gastroenterol Hepatol. 2015;12(5):271–83.CrossRefPubMed
9.
go back to reference Salminen A, Kaarniranta K, Kauppinen A. Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging (Albany NY). 2012;4(3):166–75. Salminen A, Kaarniranta K, Kauppinen A. Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging (Albany NY). 2012;4(3):166–75.
10.
go back to reference Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013;13(6):397–411.CrossRefPubMed Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013;13(6):397–411.CrossRefPubMed
11.
go back to reference Kono H, Kimura Y, Latz E. Inflammasome activation in response to dead cells and their metabolites. Curr Opin Immunol. 2014;30:91–8.CrossRefPubMed Kono H, Kimura Y, Latz E. Inflammasome activation in response to dead cells and their metabolites. Curr Opin Immunol. 2014;30:91–8.CrossRefPubMed
12.
go back to reference Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357–61.PubMedCentralCrossRefPubMed Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357–61.PubMedCentralCrossRefPubMed
13.
go back to reference Dihlmann S, Erhart P, Mehrabi A, Nickkholgh A, Lasitschka F, Böckler D, et al. Increased expression and activation of absent in melanoma 2 inflammasome components in lymphocytic infiltrates of abdominal aortic aneurysms. Mol Med. 2014;20(1):230–7.PubMedCentralCrossRefPubMed Dihlmann S, Erhart P, Mehrabi A, Nickkholgh A, Lasitschka F, Böckler D, et al. Increased expression and activation of absent in melanoma 2 inflammasome components in lymphocytic infiltrates of abdominal aortic aneurysms. Mol Med. 2014;20(1):230–7.PubMedCentralCrossRefPubMed
14.
go back to reference Hakimi M, Peters A, Becker A, Böckler D, Dihlmann S. Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis. J Vasc Surg. 2014;59(3):794–803. e2.CrossRefPubMed Hakimi M, Peters A, Becker A, Böckler D, Dihlmann S. Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis. J Vasc Surg. 2014;59(3):794–803. e2.CrossRefPubMed
15.
go back to reference Samstad EO, Niyonzima N, Nymo S, Aune MH, Ryan L, Bakke SS, et al. Cholesterol crystals induce complement-dependent inflammasome activation and cytokine release. J Immunol. 2014;192(6):2837–45.PubMedCentralCrossRefPubMed Samstad EO, Niyonzima N, Nymo S, Aune MH, Ryan L, Bakke SS, et al. Cholesterol crystals induce complement-dependent inflammasome activation and cytokine release. J Immunol. 2014;192(6):2837–45.PubMedCentralCrossRefPubMed
16.
go back to reference Golledge AL, Walker P, Norman PE, Golledge J. A systematic review of studies examining inflammation associated cytokines in human abdominal aortic aneurysm samples. Dis Markers. 2009;26(4):181–8.PubMedCentralCrossRefPubMed Golledge AL, Walker P, Norman PE, Golledge J. A systematic review of studies examining inflammation associated cytokines in human abdominal aortic aneurysm samples. Dis Markers. 2009;26(4):181–8.PubMedCentralCrossRefPubMed
17.
go back to reference Youm YH, Grant RW, McCabe LR, Albarado DC, Nguyen KY, Ravussin A, et al. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metab. 2013;18(4):519–32.PubMedCentralCrossRefPubMed Youm YH, Grant RW, McCabe LR, Albarado DC, Nguyen KY, Ravussin A, et al. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metab. 2013;18(4):519–32.PubMedCentralCrossRefPubMed
18.
go back to reference Spencer NF, Poynter ME, Im SY, Daynes RA. Constitutive activation of NF-kappa B in an animal model of aging. Int Immunol. 1997;9(10):1581–8.CrossRefPubMed Spencer NF, Poynter ME, Im SY, Daynes RA. Constitutive activation of NF-kappa B in an animal model of aging. Int Immunol. 1997;9(10):1581–8.CrossRefPubMed
19.
go back to reference Xiao ZQ, Majumdar AP. Induction of transcriptional activity of AP-1 and NF-kappaB in the gastric mucosa during aging. Am J Physiol Gastrointest Liver Physiol. 2000;278(6):G855–65.PubMed Xiao ZQ, Majumdar AP. Induction of transcriptional activity of AP-1 and NF-kappaB in the gastric mucosa during aging. Am J Physiol Gastrointest Liver Physiol. 2000;278(6):G855–65.PubMed
20.
go back to reference Helenius M, Kyrylenko S, Vehviläinen P, Salminen A. Characterization of aging-associated up-regulation of constitutive nuclear factor-kappa B binding activity. Antioxid Redox Signal. 2001;3(1):147–56.CrossRefPubMed Helenius M, Kyrylenko S, Vehviläinen P, Salminen A. Characterization of aging-associated up-regulation of constitutive nuclear factor-kappa B binding activity. Antioxid Redox Signal. 2001;3(1):147–56.CrossRefPubMed
21.
go back to reference Duan X, Ponomareva L, Veeranki S, Panchanathan R, Dickerson E, Choubey D. Differential Roles for the Interferon-Inducible IFI16 and AIM2 Innate Immune Sensors for Cytosolic DNA in Cellular Senescence of Human Fibroblasts. Mol Cancer Res. 2011;9(5):589–602.PubMedCentralCrossRefPubMed Duan X, Ponomareva L, Veeranki S, Panchanathan R, Dickerson E, Choubey D. Differential Roles for the Interferon-Inducible IFI16 and AIM2 Innate Immune Sensors for Cytosolic DNA in Cellular Senescence of Human Fibroblasts. Mol Cancer Res. 2011;9(5):589–602.PubMedCentralCrossRefPubMed
22.
go back to reference Della Bella S, Bierti L, Presicce P, Arienti R, Valenti M, Saresella M, et al. Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol. 2007;122(2):220–8.CrossRefPubMed Della Bella S, Bierti L, Presicce P, Arienti R, Valenti M, Saresella M, et al. Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol. 2007;122(2):220–8.CrossRefPubMed
23.
go back to reference Lorton D, Bellinger DL. Molecular mechanisms underlying beta-adrenergic receptor-mediated cross-talk between sympathetic neurons and immune cells. Int J Mol Sci. 2015;16(3):5635–65.PubMedCentralCrossRefPubMed Lorton D, Bellinger DL. Molecular mechanisms underlying beta-adrenergic receptor-mediated cross-talk between sympathetic neurons and immune cells. Int J Mol Sci. 2015;16(3):5635–65.PubMedCentralCrossRefPubMed
24.
go back to reference Santulli G, Iaccarino G. Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes. Immun Ageing. 2013;10(1):10.PubMedCentralCrossRefPubMed Santulli G, Iaccarino G. Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes. Immun Ageing. 2013;10(1):10.PubMedCentralCrossRefPubMed
Metadata
Title
Gene expression of inflammasome components in peripheral blood mononuclear cells (PBMC) of vascular patients increases with age
Authors
Xiaoyu Wu
Maani Hakimi
Markus Wortmann
Jian Zhang
Dittmar Böckler
Susanne Dihlmann
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2015
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-015-0043-y

Other articles of this Issue 1/2015

Immunity & Ageing 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.