nach oben

Erschienen in:

22.07.2022 | Original Article

Angiotensin II Triggers NLRP3 Inflammasome Activation by a Ca²⁺ Signaling-Dependent Pathway in Rat Cardiac Fibroblast Ang-II by a Ca²⁺-Dependent Mechanism Triggers NLRP3 Inflammasome in CF

verfasst von: Jenaro Antonio Espitia-Corredor, Pía Boza, Claudio Espinoza-Pérez, José Miguel Lillo, Constanza Rimassa-Taré, Víctor Machuca, José Miguel Osorio-Sandoval, Raúl Vivar, Samir Bolivar, Viviana Pardo-Jiménez, Carlos Félix Sánchez-Ferrer, Concepción Peiró, Guillermo Díaz-Araya

Erschienen in: Inflammation | Ausgabe 6/2022

Einloggen, um Zugang zu erhalten

Abstract

Angiotensin II (Ang-II) is a widely studied hypertensive, profibrotic, and pro-inflammatory peptide. In the heart, cardiac fibroblasts (CF) express type 1 angiotensin II receptors (AT1R), Toll-like receptor-4 (TLR4), and the NLRP3 inflammasome complex, which play important roles in pro-inflammatory processes. When activated, the NLRP3 inflammasome triggers proteolytic cleavage of pro-IL-1, resulting in its activation. However, in CF the mechanism by which Ang-II assembles and activates the NLRP3 inflammasome remains not fully known. To elucidate this important point, we stimulated TLR4 receptors in CF and evaluated the signaling pathways by which Ang-II triggers the assembly and activity. In cultured rat CF, pro-IL-1β levels, NLRP3, ASC, and caspase-1 expression levels were determined by Western blot. NLRP3 inflammasome complex assembly was analyzed by immunocytochemistry, whereas by ELISA, we analyzed NLRP3 inflammasome activity and \(IL-1\beta\) release. In CF, Ang-II triggered NLRP3 inflammasome assembly and caspase-1 activity; and in LPS-pretreated CF, Ang-II also triggered \(IL-1\beta\) secretion. These effects were blocked by losartan (AT1R antagonist), U73221 (PLC inhibitor), 2-APB (IP3R antagonist), and BAPTA-AM (Ca²⁺ chelator) indicating that the AT1R/PLC/IP3R/Ca²⁺ pathway is involved. Finally, bafilomycin A1 prevented Ang-II-induced \(IL-1\beta\) secretion, indicating that a non-classical protein secretion mechanism is involved. These findings suggest that in CF, Ang-II by a Ca²⁺-dependent mechanism triggers NLRP3 inflammasome assembly and activation leading to \(IL-1\beta\) secretion through a non-conventional protein secretion mechanism.

Nur mit Berechtigung zugänglich

Forrester, S.J., G.W. Booz, C.D. Sigmund, T.M. Coffman, T. Kawai, V. Rizzo, R. Scalia, and S. Eguchi. 2018. Angiotensin II signal transduction: an update on mechanisms of physiology and pathophysiology. Physiological Reviews 98: 1627–1738. https://doi.org/10.1152/physrev.00038.2017.CrossRefPubMedPubMedCentral

Wu, Y., Y. Li, C. Zhang, Y. Wang, W. Cui, H. Li, and J. Du. 2014. S100a8/a9 released by CD11b+Gr1+ neutrophils activates cardiac fibroblasts to initiate angiotensin II–induced cardiac inflammation and injury. Hypertension 63: 1241–1250. https://doi.org/10.1161/HYPERTENSIONAHA.113.02843.CrossRefPubMed

Wang, M., L. Jiang, R.E. Monticone, and E.G. Lakatta. 2014. Proinflammation: the key to arterial aging. Trends in Endocrinology & Metabolism 25: 72–79. https://doi.org/10.1016/j.tem.2013.10.002.CrossRef

Cheng, Z.J., H. Vapaatalo, and E. Mervaala. 2005. Angiotensin II and vascular inflammation. Med Sci Monit 11: Ra194–205.

Gan, W., J. Ren, T. Li, S. Lv, C. Li, Z. Liu, and M. Yang. 2018. The SGK1 inhibitor EMD638683, prevents angiotensin II–induced cardiac inflammation and fibrosis by blocking NLRP3 inflammasome activation. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1864: 1–10. https://doi.org/10.1016/j.bbadis.2017.10.001.

Kawaguchi, M., M. Takahashi, T. Hata, Y. Kashima, F. Usui, H. Morimoto, A. Izawa, Y. Takahashi, J. Masumoto, J. Koyama, M. Hongo, T. Noda, J. Nakayama, J. Sagara, and Taniguchi, S.i. and Ikeda, U. 2011. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation 123: 594–604. https://doi.org/10.1161/CIRCULATIONAHA.110.982777.CrossRefPubMed

Sandanger, Ø., T. Ranheim, L.E. Vinge, M. Bliksøen, K. Alfsnes, A.V. Finsen, C.P. Dahl, E.T. Askevold, G. Florholmen, G. Christensen, K.A. Fitzgerald, E. Lien, G. Valen, T. Espevik, P. Aukrust, and A. Yndestad. 2013. The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia–reperfusion injury. Cardiovascular Research 99: 164–174. https://doi.org/10.1093/cvr/cvt091.CrossRefPubMed

Palmer, J.N., W.E. Hartogensis, M. Patten, F.D. Fortuin, and C.S. Long. 1995. Interleukin-1 beta induces cardiac myocyte growth but inhibits cardiac fibroblast proliferation in culture. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI117956.CrossRefPubMedPubMedCentral

Abbate, A., S. Toldo, C. Marchetti, J. Kron, B.W. Van Tassell, and C.A. Dinarello. 2020. Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease. Circulation Research 126: 1260–1280. https://doi.org/10.1161/CIRCRESAHA.120.315937.CrossRefPubMedPubMedCentral

10.

Takahashi, M. 2019. Role of NLRP3 inflammasome in cardiac inflammation and remodeling after myocardial infarction. Biological and Pharmaceutical Bulletin 42: 518–523. https://doi.org/10.1248/bpb.b18-00369.CrossRefPubMed

11.

Xiao, H., H. Li, J.-J. Wang, J.-S. Zhang, J. Shen, X.-B. An, C.-C. Zhang, J.-M. Wu, Y. Song, X.-Y. Wang, H.-Y. Yu, X.-N. Deng, Z.-J. Li, M. Xu, Z.-Z. Lu, J. Du, W. Gao, A.-H. Zhang, Y. Feng, and Y.-Y. Zhang. 2018. IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult. European Heart Journal 39: 60–69. https://doi.org/10.1093/eurheartj/ehx261.CrossRefPubMed

12.

Abderrazak, A., T. Syrovets, D. Couchie, K. El Hadri, B. Friguet, T. Simmet, and M. Rouis. 2015. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biology 4: 296–307. https://doi.org/10.1016/j.redox.2015.01.008.CrossRefPubMedPubMedCentral

13.

Man, S.M., and T.-D. Kanneganti. 2015. Regulation of inflammasome activation. Immunological Reviews 265: 6–21. https://doi.org/10.1111/imr.12296.CrossRefPubMedPubMedCentral

14.

Diaz-Araya, G., R. Vivar, C. Humeres, P. Boza, S. Bolivar, and C. Munoz. 2015. Cardiac fibroblasts as sentinel cells in cardiac tissue: receptors, signaling pathways and cellular functions. Pharmacological Research 101: 30–40. https://doi.org/10.1016/j.phrs.2015.07.001.CrossRefPubMed

15.

Aránguiz-Urroz, P., D. Soto, A. Contreras, R. Troncoso, M. Chiong, J. Montenegro, D. Venegas, C. Smolic, P. Ayala, W.G. Thomas, S. Lavandero, and G. Díaz-Araya. 2009. Differential participation of angiotensin II type 1 and 2 receptors in the regulation of cardiac cell death triggered by angiotensin II. American Journal of Hypertension 22: 569–576. https://doi.org/10.1038/ajh.2009.32.CrossRefPubMed

16.

Vivar, R., C. Soto, M. Copaja, F. Mateluna, P. Aranguiz, J.P. Muñoz, M. Chiong, L. Garcia, A. Letelier, W.G. Thomas, S. Lavandero, and G. Díaz-Araya. 2008. Phospholipase C/protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor. Journal of Cardiovascular Pharmacology. https://doi.org/10.1097/FJC.0b013e318181fadd.CrossRefPubMed

17.

Boza, P., P. Ayala, R. Vivar, C. Humeres, F.T. Cáceres, C. Muñoz, L. García, M.A. Hermoso, and G. Díaz-Araya. 2016. Expression and function of toll-like receptor 4 and inflammasomes in cardiac fibroblasts and myofibroblasts: IL-1β synthesis, secretion, and degradation. Molecular Immunology 74: 96–105. https://doi.org/10.1016/j.molimm.2016.05.001.CrossRefPubMed

18.

Turner, N.A. 2016. Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs). Journal of Molecular and Cellular Cardiology 94: 189–200. https://doi.org/10.1016/j.yjmcc.2015.11.002.CrossRefPubMed

19.

Bolívar, S., R. Santana, P. Ayala, R. Landaeta, P. Boza, C. Humeres, R. Vivar, C. Muñoz, V. Pardo, S. Fernandez, R. Anfossi, and G. Diaz-Araya. 2017. Lipopolysaccharide activates Toll-like receptor 4 and prevents cardiac fibroblast-to-myofibroblast differentiation. Cardiovascular Toxicology 17: 458–470. https://doi.org/10.1007/s12012-017-9404-4.CrossRefPubMed

20.

Olivares-Silva, F., R. Landaeta, P. Aranguiz, S. Bolivar, C. Humeres, R. Anfossi, R. Vivar, P. Boza, C. Munoz, V. Pardo-Jimenez, C. Peiro, C.F. Sanchez-Ferrer, and G. Diaz-Araya. 2018. Heparan sulfate potentiates leukocyte adhesion on cardiac fibroblast by enhancing Vcam-1 and Icam-1 expression. Biochimica et Biophysica Acta, Molecular Basis of Disease 1864: 831–842. https://doi.org/10.1016/j.bbadis.2017.12.002.CrossRefPubMed

21.

Humeres, C., R. Vivar, P. Boza, C. Munoz, S. Bolivar, R. Anfossi, J.M. Osorio, F. Olivares-Silva, L. Garcia, and G. Diaz-Araya. 2016. Cardiac fibroblast cytokine profiles induced by proinflammatory or profibrotic stimuli promote monocyte recruitment and modulate macrophage M1/M2 balance in vitro. Journal of Molecular and Cellular Cardiology. https://doi.org/10.1016/j.yjmcc.2016.10.014.CrossRefPubMed

22.

Bracey, N.A., B. Gershkovich, J. Chun, A. Vilaysane, H.C. Meijndert, J.R. Wright Jr., P.W. Fedak, P.L. Beck, D.A. Muruve, and H.J. Duff. 2014. Mitochondrial NLRP3 protein induces reactive oxygen species to promote Smad protein signaling and fibrosis independent from the inflammasome *. Journal of Biological Chemistry 289: 19571–19584. https://doi.org/10.1074/jbc.M114.550624.CrossRefPubMedPubMedCentral

23.

Gombault, A., L. Baron, and I. Couillin. 2013. ATP release and purinergic signaling in NLRP3 inflammasome activation. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2012.00414.CrossRefPubMedPubMedCentral

24.

Li, J., X. Teng, S. Jin, J. Dong, Q. Guo, D. Tian, and Y. Wu. 2019. Hydrogen sulfide improves endothelial dysfunction by inhibiting the vicious cycle of NLRP3 inflammasome and oxidative stress in spontaneously hypertensive rats. Journal of Hypertension 37: 1. https://doi.org/10.1097/HJH.0000000000002101.CrossRef

25.

Zhou, B., Y. Qiu, N. Wu, A.-D. Chen, H. Zhou, Q. Chen, Y.-M. Kang, Y.-H. Li, and G.-Q. Zhu. 2020. FNDC5 attenuates oxidative stress and NLRP3 inflammasome activation in vascular smooth muscle cells via activating the AMPK-SIRT1 signal pathway. Oxidative Medicine and Cellular Longevity 2020: 6384803. https://doi.org/10.1155/2020/6384803.CrossRefPubMedPubMedCentral

26.

Bryan, N.B., A. Dorfleutner, Y. Rojanasakul, and C. Stehlik. 2009. Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain. The Journal of Immunology 182: 3173. https://doi.org/10.4049/jimmunol.0802367.CrossRefPubMed

27.

Jo, E.-K., J.K. Kim, D.-M. Shin, and C. Sasakawa. 2016. Molecular mechanisms regulating NLRP3 inflammasome activation. Cellular & Molecular Immunology 13: 148–159. https://doi.org/10.1038/cmi.2015.95.CrossRef

28.

Liang, Y.-D., W.-J. Bai, C.-G. Li, L.-H. Xu, H.-X. Wei, H. Pan, X.-H. He, and D.-Y. Ouyang. 2016. Piperine suppresses pyroptosis and interleukin-1β release upon ATP triggering and bacterial infection. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2016.00390.CrossRefPubMedPubMedCentral

29.

Guo, H., J.B. Callaway, and J.P.Y. Ting. 2015. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nature medicine 21: 677–687. https://doi.org/10.1038/nm.3893.CrossRefPubMedPubMedCentral

30.

Netea, M.G., A. Simon, F. van de Veerdonk, B.-J. Kullberg, J.W.M. Van der Meer, and L.A.B. Joosten. 2010. IL-1β processing in host defense: beyond the inflammasomes. PLOS Pathogens 6: e1000661. https://doi.org/10.1371/journal.ppat.1000661.

31.

Rossol, M., M. Pierer, N. Raulien, D. Quandt, U. Meusch, K. Rothe, K. Schubert, T. Schöneberg, M. Schaefer, U. Krügel, S. Smajilovic, H. Bräuner-Osborne, C. Baerwald, and U. Wagner. 2012. Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors. Nature communications 3: 1329–1329. https://doi.org/10.1038/ncomms2339.CrossRefPubMed

32.

Wang, F., L. Huang, Z.Z. Peng, Y.T. Tang, M.M. Lu, Y. Peng, W.J. Mel, L. Wu, Z.H. Mo, J. Meng, and L.J. Tao. 2014. Losartan inhibits LPS + ATP-induced IL-1beta secretion from mouse primary macrophages by suppressing NALP3 inflammasome. Die Pharmazie 69: 680–684. https://doi.org/10.1691/ph.2014.3926.CrossRefPubMed

33.

Usui, F., K. Shirasuna, H. Kimura, K. Tatsumi, A. Kawashima, T. Karasawa, K. Yoshimura, H. Aoki, H. Tsutsui, T. Noda, J. Sagara, and Taniguchi, S.i. and Takahashi, M. 2015. Inflammasome activation by mitochondrial oxidative stress in macrophages leads to the development of angiotensin II–induced aortic aneurysm. Arteriosclerosis, Thrombosis, and Vascular Biology 35: 127–136. https://doi.org/10.1161/ATVBAHA.114.303763.CrossRefPubMed

34.

Horng, T. 2014. Calcium signaling and mitochondrial destabilization in the triggering of the NLRP3 inflammasome. Trends in Immunology 35: 253–261. https://doi.org/10.1016/j.it.2014.02.007.CrossRefPubMedPubMedCentral

35.

Zhang, L.-L., S. Huang, X.-X. Ma, W.-Y. Zhang, D. Wang, S.-Y. Jin, Y.-P. Zhang, Y. Li, and X. Li. 2016. Angiotensin(1–7) attenuated angiotensin II-induced hepatocyte EMT by inhibiting NOX-derived H2O2-activated NLRP3 inflammasome/IL-1β/Smad circuit. Free Radical Biology and Medicine 97: 531–543. https://doi.org/10.1016/j.freeradbiomed.2016.07.014.CrossRefPubMed

36.

Zhao, M., M. Bai, G. Ding, Y. Zhang, S. Huang, Z. Jia, and A. Zhang. 2018. Angiotensin II stimulates the NLRP3 inflammasome to induce podocyte injury and mitochondrial dysfunction. Kidney Diseases 4: 83–94. https://doi.org/10.1159/000488242.CrossRefPubMedPubMedCentral

37.

Malhotra, V. 2013. Unconventional protein secretion: an evolving mechanism. The EMBO Journal 32: 1660–1664. https://doi.org/10.1038/emboj.2013.104.CrossRefPubMedPubMedCentral

38.

Lopez-Castejon, G., and D. Brough. 2011. Understanding the mechanism of IL-1β secretion. Cytokine & Growth Factor Reviews 22: 189–195. https://doi.org/10.1016/j.cytogfr.2011.10.001.CrossRef

39.

Eder, C. 2009. Mechanisms of interleukin-1β release. Immunobiology 214: 543–553. https://doi.org/10.1016/j.imbio.2008.11.007.CrossRefPubMed

40.

Qu, Y., L. Franchi, G. Nunez, and G.R. Dubyak. 2007. Nonclassical IL-1β secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. The Journal of Immunology 179: 1913. https://doi.org/10.4049/jimmunol.179.3.1913.CrossRefPubMed

41.

Piccioli, P., and A. Rubartelli. 2013. The secretion of IL-1β and options for release. Seminars in Immunology 25: 425–429. https://doi.org/10.1016/j.smim.2013.10.007.CrossRefPubMed

42.

Katsnelson, M., L. Rucker, H. Russo, and G. Dubyak. (2015). K+ Efflux agonists induce NLRP3 inflammasome activation independently of Ca2+ signaling. Journal of immunology (Baltimore, Md. : 1950) 194. https://doi.org/10.4049/jimmunol.1402658.

43.

Galliher-Beckley, A.J., L.-Q. Lan, S. Aono, L. Wang, and J. Shi. 2013. Caspase-1 activation and mature interleukin-1β release are uncoupled events in monocytes. World journal of biological chemistry 4: 30–34. https://doi.org/10.4331/wjbc.v4.i2.30.CrossRefPubMedPubMedCentral

44.

Butts, B., R.A. Gary, S.B. Dunbar, and J. Butler. 2015. The importance of NLRP3 inflammasome in heart failure. Journal of Cardiac Failure 21: 586–593. https://doi.org/10.1016/j.cardfail.2015.04.014.CrossRefPubMedPubMedCentral

Titel: Angiotensin II Triggers NLRP3 Inflammasome Activation by a Ca2+ Signaling-Dependent Pathway in Rat Cardiac Fibroblast Ang-II by a Ca2+-Dependent Mechanism Triggers NLRP3 Inflammasome in CF
verfasst von: Jenaro Antonio Espitia-Corredor
Pía Boza
Claudio Espinoza-Pérez
José Miguel Lillo
Constanza Rimassa-Taré
Víctor Machuca
José Miguel Osorio-Sandoval
Raúl Vivar
Samir Bolivar
Viviana Pardo-Jiménez
Carlos Félix Sánchez-Ferrer
Concepción Peiró
Guillermo Díaz-Araya
Publikationsdatum: 22.07.2022
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 6/2022
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-022-01707-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Angiotensin II Triggers NLRP3 Inflammasome Activation by a Ca²⁺ Signaling-Dependent Pathway in Rat Cardiac Fibroblast Ang-II by a Ca²⁺-Dependent Mechanism Triggers NLRP3 Inflammasome in CF

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

Antikörper mobilisiert Neutrophile gegen Krebs

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2022

Basiliximab Does Not Impair Airway Mucociliary Clearance of Rats

Cannabinoid Analogue WIN 55212–2 Protects Paraquat-Induced Lung Injury and Enhances Macrophage M2 Polarization

Pectolinarigenin Suppresses LPS-Induced Inflammatory Response in Macrophages and Attenuates DSS-Induced Colitis by Modulating the NF-κB/Nrf2 Signaling Pathway

The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients

Gallic Acid Improves Therapeutic Effects of Mesenchymal Stem Cells Derived from Adipose Tissue in Acute Renal Injury Following Rhabdomyolysis Induced by Glycerol

Bifidobacterium bifidum and Bacteroides fragilis Induced Differential Immune Regulation of Enteric Glial Cells Subjected to Exogenous Inflammatory Stimulation

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

Antikörper mobilisiert Neutrophile gegen Krebs

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

Update Innere Medizin