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The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis.
Pancreatology 2017 May - Jun; 17(3):364-371P

Abstract

BACKGROUND

Acute pancreatitis is an inflammatory disorder of the pancreas that is responsible for significant morbidity and mortality. The inflammasome pathway has acquired significant relevance in the pathogenesis of many inflammatory disorders, but its role in patients with acute pancreatitis still awaits clarification.

METHODS

We performed a prospective study in which 27 patients with acute pancreatitis and 16 healthy controls were included. We isolated peripheral blood mononuclear cells (PBMCs) and we assessed the expression and activation of different inflammasomes as well as their association with the clinical course of the disease.

RESULTS

Our results show that PBMCs from patients with acute pancreatitis have elevated expression of several components of the inflammasome complex, including the inflammasome-forming receptor absent in melanoma 2 (AIM2), early during the onset of the disease. Activation of the AIM2 or NLRP3 inflammasomes in PBMCs from patients with acute pancreatitis results in exacerbated IL-1β and IL-18 production compared with PBMCs from healthy controls. Furthermore, both AIM2 mRNA expression and AIM2-mediated production of IL-1β by PBMCs correlated with increased systemic inflammation in these patients. Last, AIM2 expression was further increased in those patients that developed transient or persistent organ failure (moderate or severe acute pancreatitis).

CONCLUSIONS

Our data demonstrates that AIM2 inflammasome expression and activation is increased early during the course of acute pancreatitis, and suggests that AIM2 activation may affect systemic inflammation and organ failure in these patients.

Authors+Show Affiliations

Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain.Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain; Department of Gastroenterology, General Hospital of Alicante, Alicante, Spain.Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain; Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain.Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain; Department of Pharmacology, University Miguel Hernández, Alicante, Spain.Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain; Department of Gastroenterology, General Hospital of Alicante, Alicante, Spain.Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain.Hematology Service, General Hospital of Alicante, Alicante, Spain.Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain; Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain; Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain; Department of Clinical Medicine, University Miguel Hernández, Alicante, Spain.Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain; Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain; Department of Pharmacology, University Miguel Hernández, Alicante, Spain.Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain; Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain. Electronic address: gonzalez_josnav@gva.es.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28342645

Citation

Algaba-Chueca, Francisco, et al. "The Expression and Activation of the AIM2 Inflammasome Correlates With Inflammation and Disease Severity in Patients With Acute Pancreatitis." Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.], vol. 17, no. 3, 2017, pp. 364-371.
Algaba-Chueca F, de-Madaria E, Lozano-Ruiz B, et al. The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis. Pancreatology. 2017;17(3):364-371.
Algaba-Chueca, F., de-Madaria, E., Lozano-Ruiz, B., Martínez-Cardona, C., Quesada-Vázquez, N., Bachiller, V., ... González-Navajas, J. M. (2017). The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis. Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.], 17(3), pp. 364-371. doi:10.1016/j.pan.2017.03.006.
Algaba-Chueca F, et al. The Expression and Activation of the AIM2 Inflammasome Correlates With Inflammation and Disease Severity in Patients With Acute Pancreatitis. Pancreatology. 2017;17(3):364-371. PubMed PMID: 28342645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis. AU - Algaba-Chueca,Francisco, AU - de-Madaria,Enrique, AU - Lozano-Ruiz,Beatriz, AU - Martínez-Cardona,Claudia, AU - Quesada-Vázquez,Noé, AU - Bachiller,Victoria, AU - Tarín,Fabián, AU - Such,José, AU - Francés,Rubén, AU - Zapater,Pedro, AU - González-Navajas,José M, Y1 - 2017/03/18/ PY - 2016/09/22/received PY - 2017/03/14/revised PY - 2017/03/16/accepted PY - 2017/3/28/pubmed PY - 2018/3/20/medline PY - 2017/3/27/entrez KW - Inflammasomes KW - Inflammatory mediators KW - Innate immunity KW - Pancreatitis SP - 364 EP - 371 JF - Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] JO - Pancreatology VL - 17 IS - 3 N2 - BACKGROUND: Acute pancreatitis is an inflammatory disorder of the pancreas that is responsible for significant morbidity and mortality. The inflammasome pathway has acquired significant relevance in the pathogenesis of many inflammatory disorders, but its role in patients with acute pancreatitis still awaits clarification. METHODS: We performed a prospective study in which 27 patients with acute pancreatitis and 16 healthy controls were included. We isolated peripheral blood mononuclear cells (PBMCs) and we assessed the expression and activation of different inflammasomes as well as their association with the clinical course of the disease. RESULTS: Our results show that PBMCs from patients with acute pancreatitis have elevated expression of several components of the inflammasome complex, including the inflammasome-forming receptor absent in melanoma 2 (AIM2), early during the onset of the disease. Activation of the AIM2 or NLRP3 inflammasomes in PBMCs from patients with acute pancreatitis results in exacerbated IL-1β and IL-18 production compared with PBMCs from healthy controls. Furthermore, both AIM2 mRNA expression and AIM2-mediated production of IL-1β by PBMCs correlated with increased systemic inflammation in these patients. Last, AIM2 expression was further increased in those patients that developed transient or persistent organ failure (moderate or severe acute pancreatitis). CONCLUSIONS: Our data demonstrates that AIM2 inflammasome expression and activation is increased early during the course of acute pancreatitis, and suggests that AIM2 activation may affect systemic inflammation and organ failure in these patients. SN - 1424-3911 UR - https://www.unboundmedicine.com/medline/citation/28342645/The_expression_and_activation_of_the_AIM2_inflammasome_correlates_with_inflammation_and_disease_severity_in_patients_with_acute_pancreatitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1424-3903(17)30061-3 DB - PRIME DP - Unbound Medicine ER -