Tags

Type your tag names separated by a space and hit enter

AIM2/IL-1α/TGF-β Axis in PBMCs From Exacerbated Chronic Obstructive Pulmonary Disease (COPD) Patients Is Not Related to COX-2-Dependent Inflammatory Pathway.
Front Physiol 2019; 10:1235FP

Abstract

Chronic obstructive pulmonary disease (COPD) is a lung disorder characterized by persistent respiratory symptoms and progressive airflow limitation as a consequence of a chronic inflammatory response. Corticosteroids are the main treatment for COPD patients with a history of exacerbation, in that they attenuate exacerbation and dyspnea, and improve the response to bronchodilators. Nevertheless, despite corticosteroid administration, COPD patients still undergo exacerbation phases. In this context, the aim of this study was to evaluate the activity of Absent in melanoma 2 (AIM2) inflammasome-dependent pathways under corticosteroid treatment during COPD exacerbation. Stable and exacerbated COPD-derived Peripheral Blood Mononuclear Cells (PBMCs) were treated with a well-known anti-inflammatory agent, Dexamethasone (DEX), in the presence or not of Poly (deoxyadenylic-deoxythymidylate) acid (Poly dA:dT), an AIM2 ligand. We found that IL-1α was highly increased when AIM2 was activated from Poly dA:dT in exacerbated, but not in stable, COPD-derived PBMCs. To note, the release of IL-1α after the stimulation of AIM2 in PBMCs obtained from stable (hospitalized) COPD patients was not higher from the basal conditions, though it was still as high as that observed for Poly dA:dT-stimulated PBMCs obtained from exacerbated patients. This effect was associated with a higher expression of AIM2 in pair-matched circulating CD14+ cells obtained from hospitalized patients who passed from the exacerbation to stable status. Because the difference between stable and exacerbated COPD patients relies on the treatment with corticosteroids, exacerbated and stable COPD-derived PBMCs were treated with DEX. Indeed, the release of IL-1α and TGF-β was not altered after DEX treatment. In conclusion, we found that the administration of DEX in vitro on exacerbated COPD-derived PBMCs was not able to revert the detrimental inflammatory mechanism associated with AIM2 activation responsible for the release of IL-1α and the ensuing TGF-β, contributing to the severity of disease.

Authors+Show Affiliations

Department of Respiratory Medicine, Respiratory Division, University of Naples Federico II, Naples, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy. Ph.D. Program in Drug Discovery and Development, Department of Pharmacy, University of Salerno, Fisciano, Italy.Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.Department of Anatomy and Pathology, Ospedale dei Colli "Monaldi-CTO", Naples, Italy.Department of Respiratory Medicine, Respiratory Division, University of Naples Federico II, Naples, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy.Department of Pharmacy, University of Salerno, Fisciano, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31632288

Citation

Molino, Antonio, et al. "AIM2/IL-1α/TGF-β Axis in PBMCs From Exacerbated Chronic Obstructive Pulmonary Disease (COPD) Patients Is Not Related to COX-2-Dependent Inflammatory Pathway." Frontiers in Physiology, vol. 10, 2019, p. 1235.
Molino A, Terlizzi M, Colarusso C, et al. AIM2/IL-1α/TGF-β Axis in PBMCs From Exacerbated Chronic Obstructive Pulmonary Disease (COPD) Patients Is Not Related to COX-2-Dependent Inflammatory Pathway. Front Physiol. 2019;10:1235.
Molino, A., Terlizzi, M., Colarusso, C., Rossi, A., Somma, P., Saglia, A., ... Sorrentino, R. (2019). AIM2/IL-1α/TGF-β Axis in PBMCs From Exacerbated Chronic Obstructive Pulmonary Disease (COPD) Patients Is Not Related to COX-2-Dependent Inflammatory Pathway. Frontiers in Physiology, 10, p. 1235. doi:10.3389/fphys.2019.01235.
Molino A, et al. AIM2/IL-1α/TGF-β Axis in PBMCs From Exacerbated Chronic Obstructive Pulmonary Disease (COPD) Patients Is Not Related to COX-2-Dependent Inflammatory Pathway. Front Physiol. 2019;10:1235. PubMed PMID: 31632288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AIM2/IL-1α/TGF-β Axis in PBMCs From Exacerbated Chronic Obstructive Pulmonary Disease (COPD) Patients Is Not Related to COX-2-Dependent Inflammatory Pathway. AU - Molino,Antonio, AU - Terlizzi,Michela, AU - Colarusso,Chiara, AU - Rossi,Antonietta, AU - Somma,Pasquale, AU - Saglia,Alessandro, AU - Pinto,Aldo, AU - Sorrentino,Rosalinda, Y1 - 2019/10/01/ PY - 2019/06/06/received PY - 2019/09/09/accepted PY - 2019/10/22/entrez PY - 2019/10/22/pubmed PY - 2019/10/22/medline KW - COPD KW - IL-1-like cytokines KW - chronic lung inflammation KW - inflammasome KW - lung SP - 1235 EP - 1235 JF - Frontiers in physiology JO - Front Physiol VL - 10 N2 - Chronic obstructive pulmonary disease (COPD) is a lung disorder characterized by persistent respiratory symptoms and progressive airflow limitation as a consequence of a chronic inflammatory response. Corticosteroids are the main treatment for COPD patients with a history of exacerbation, in that they attenuate exacerbation and dyspnea, and improve the response to bronchodilators. Nevertheless, despite corticosteroid administration, COPD patients still undergo exacerbation phases. In this context, the aim of this study was to evaluate the activity of Absent in melanoma 2 (AIM2) inflammasome-dependent pathways under corticosteroid treatment during COPD exacerbation. Stable and exacerbated COPD-derived Peripheral Blood Mononuclear Cells (PBMCs) were treated with a well-known anti-inflammatory agent, Dexamethasone (DEX), in the presence or not of Poly (deoxyadenylic-deoxythymidylate) acid (Poly dA:dT), an AIM2 ligand. We found that IL-1α was highly increased when AIM2 was activated from Poly dA:dT in exacerbated, but not in stable, COPD-derived PBMCs. To note, the release of IL-1α after the stimulation of AIM2 in PBMCs obtained from stable (hospitalized) COPD patients was not higher from the basal conditions, though it was still as high as that observed for Poly dA:dT-stimulated PBMCs obtained from exacerbated patients. This effect was associated with a higher expression of AIM2 in pair-matched circulating CD14+ cells obtained from hospitalized patients who passed from the exacerbation to stable status. Because the difference between stable and exacerbated COPD patients relies on the treatment with corticosteroids, exacerbated and stable COPD-derived PBMCs were treated with DEX. Indeed, the release of IL-1α and TGF-β was not altered after DEX treatment. In conclusion, we found that the administration of DEX in vitro on exacerbated COPD-derived PBMCs was not able to revert the detrimental inflammatory mechanism associated with AIM2 activation responsible for the release of IL-1α and the ensuing TGF-β, contributing to the severity of disease. SN - 1664-042X UR - https://www.unboundmedicine.com/medline/citation/31632288/AIM2/IL-1α/TGF-β_Axis_in_PBMCs_From_Exacerbated_Chronic_Obstructive_Pulmonary_Disease_(COPD)_Patients_Is_Not_Related_to_COX-2-Dependent_Inflammatory_Pathway L2 - https://doi.org/10.3389/fphys.2019.01235 DB - PRIME DP - Unbound Medicine ER -